Cerebrospinal fluid viral escape in HIV patients on antiretroviral therapy: A systematic review of reported cases.

Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28-73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one-third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.

Prevalence and factors associated with viral non-suppression in people living with HIV receiving antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.

Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We determined the prevalence and factors associated with VNS for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). This review, registered with PROSPERO (CRD42023470234), conducted an extensive search for evidence, focusing on PLHIV living in SSA on ART from the year 2000 to 19th October 2023, across databases including PubMed/MEDLINE, Embase, Web of Science, and Scopus. A total of 2357 articles were screened, from which 32 studies met the criteria for the final analysis, involving 756,620 PLHIV of all ages. The pooled prevalance for VNS was found to be 20.0% (95% CI: 15.43%-25.52%, I2 = 100%, p-value <0.01) Children and adolescents demonstrated the highest prevalence of VNS (viral load ≥1000 copies/mL) at 27.98% (95% CI: 21.91%-34.97%, I2 = 94%, p-value <0.01). The study revealed various factors associated with increased odds (risk) of VNS, p-value <0.05. These factors encompassed socio-demographics such as sex, age, education level, and marital status. Additionally, aspects related to HIV care, such as the facility attended, HIV status disclosure and adherence exhibited higher odds of VNS. Suboptimal ART adherence, longer duration on ART, socio-economic factors, lack of family and social support, presence of co-morbidities, advanced WHO HIV clinical stage, ART regimens, lower CD4+ count, abnormal body mass index, history of treatment interruptions, and progression of HIV illness were associated with VNS. Furthermore, behavioural/psychological factors including depression, substance use, negative perceptions towards ART, experiences of abuse, alcohol use, stigma, and certain patterns of sexual behaviour were also identified as factors for VNS. The occurrence of two VNS to every ten PLHIV on ART poses a threat to the progress made towards reaching the third 95% UNAIDS target in SSA. Additionally, these findings highlight the intricate interplay of various factors, encompassing patient characteristics, behavioural patterns, sociocultural influences, and pharmacological factors, all impacting VNS among PLHIV. Recognising its multifaceted nature, we recommend designing and implementing high impact interventions to effectively address VNS in SSA.

Impact of differentiated service delivery models on retention in HIV care and viral suppression among people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis of randomised controlled trials.

Differentiated service delivery (DSD) models, such as adherence clubs (ACs), are client-centred approaches where clinically stable people living with HIV (PLHIV) meet to receive various services, including psychosocial support, brief symptoms screening, and refills of antiretroviral medications, among others. We conducted a review to assess the impact of DSD models, including ACs, on sustaining retention in care (RC) and achieving viral suppression (VS) among PLHIV in sub-Saharan Africa. The review protocol was registered in PROSPERO (CRD42023418988). We searched the literature from PubMed, Scopus, Web of Science, Embase and Google Scholar from their inception through May 2023. Eligible randomised controlled trials of adherence clubs were reviewed to assess impact on retention and viral suppression. Random effect models were used to estimate the risk ratios (RR) and 95% confidence intervals (CI). The literature search yielded a total of 1596 records of which 16 randomised clinical trials were determined to be eligible. The trials were conducted in diverse populations among adults and children with a total of 13,886 participants. The RR between any DSD models and standard of care (SoC) was 1.09 (95% CI: 1.08-1.11, I2 : 0%, p: <0.96) and 1.01 (95% CI: 1.00-1.02, I2 : 0%, p: <0.85) for RC and VS, respectively. The RR between ACs and SoC was 1.01 (95% CI: 0.96-1.07, I2 : 84%, p: <0.01) and 1.02 (95% CI: 0.98-1.07, I2 : 77%, p: <0.01) for RC and VS, respectively. DSD models, including ACs, show comparable effectiveness to SoC in maintaining care and achieving viral suppression for stable PLHIV. To maximise adoption, an implementation science approach is crucial for designing effective strategies and overcoming challenges.

Drivers of irrational use of antibiotics among children: a mixed-method study among prescribers and dispensers in Tanzania.

BACKGROUND: Misuse of antibiotics has been associated with poor knowledge, attitude and practice (KAP). Therefore, this study aimed to assess if KAP of prescribers and dispensers could drive irrational use of antibiotics among children in Tanzania. METHODS: A convergent parallel mixed-methods study design that employed quantitative and qualitative approaches was conducted in 14 regional referral hospitals (RRHs). A total of 108 participants, prescribers [54] and dispensers [54] working with the pediatric population in the respective regions participated in a quantitative survey, by filling the standard questionnaire while 28 key informant interviews were conducted with in-charges of units from the pharmacy and pediatric departments. Two key informants (prescriber and dispenser) were selected from each RRH. RESULTS: Overall, among prescribers and dispensers, there was adequate knowledge; 81.5% and 79.6%, p = 0.53, those with positive attitudes were 31.5% and 81.5%, p < 0.001 and poor practices were among 70.4% and 48% p = 0.0312 respectively. Among prescribers, 14.8% agreed and strongly agreed that prescribing antibiotics that a patient did not need does not contribute to resistance. Moreover 19% disagreed to prescribe antibiotics according to local guidelines. Among dispensers, a-quarter of the dispensers thought individual efforts to implement antibiotic stewardship would not make a difference, 17% agreed and strongly agreed that antibiotics can treat viral infection and 7% agreed and strongly agreed antibiotics can be stopped upon resolution of symptoms. From qualitative interviews, both participants displayed an adequate understanding of multi-contributors of antibiotic resistance (AR) including polypharmacy, community self-medication, among others. Regardless, both professions declared to prescribed and dispensed antibiotics according to the antibiotics available in stock at the facility. Furthermore, prescribers perceived laboratory investigation took a long time, hence wasting their time. On the other hand, Dispensers reported not to provide adequate instruction to the patients, after dispensing antibiotics. CONCLUSIONS: Both prescribers and dispensers had adequate knowledge, few prescribers had positive attitudes and the majority had poor practices. Few dispensers had poor attitude and practice. These findings highlight the need to provide adequate training on antimicrobial stewardship and enforce regulation that foster appropriate medical practice.

Profiling of antimicrobial dispensing practices in accredited drug dispensing outlets in Tanzania: a mixed-method cross-sectional study focusing on pediatric patients.

BACKGROUND: The emergency of antimicrobial resistance due to irrational antimicrobial use has put public health under threat. Accredited Drug Dispensing Outlets (ADDOs) play an important role in enhancing availability and accessibility of antimicrobials, however, there is a scarcity of studies assessing antimicrobial dispensing practices in these outlets, focusing on children in Tanzania. OBJECTIVE: This study was conducted to assess the antimicrobial dispensing practices among ADDO dispensers and explore the factors influencing the use of antimicrobials for children in Tanzania. METHODS: A community-based cross-sectional study utilizing both qualitative (interviews) and quantitative (simulated clients) methods was conducted between June and September 2020 in seven zones and 14 regions in Tanzania. RESULTS: The study found inappropriate dispensing and use of antimicrobials for children, influenced by multiple factors such as patient's and dispenser's knowledge and attitude, financial constraints, and product-related factors. Only 8% (62/773) of dispensers asked for prescriptions, while the majority (90%) were willing to dispense without prescriptions. Most dispensers, 83% (426/513), supplied incomplete doses of antimicrobials and only 60.5% (345/570) of the dispensers gave proper instructions for antimicrobial use to clients. Over 75% of ADDO dispensers displayed poor practice in taking patient history. CONCLUSION: ADDO dispensers demonstrated poor practices in dispensing and promoting rational antimicrobial use for children. Training, support, and regulatory interventions are required to improve antimicrobial dispensing practices in community drug outlets.

Detection profile of SARS-CoV-2 using RT-PCR in different types of clinical specimens: A systematic review and meta-analysis.

Testing is one of the commendable measures for curbing the spread of coronavirus disease (COVID-19). But, it should be done using the most appropriate specimen and an accurate diagnostic test such as real-time reverse transcription-polymerase chain reaction (qRT-PCR). Therefore, a systematic review was conducted to determine the positive detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different clinical specimens using qRT-PCR. A total of 8136 pooled clinical specimens were analyzed to detect SARS-CoV-2, the majority were nasopharyngeal swabs (69.6%). A lower respiratory tract (LRT) specimens had a positive rate (PR) of 71.3% (95% confidence interval [CI]: 60.3%-82.3%) while no virus was detected in the urinogenital specimens. Bronchoalveolar lavage fluid (BLF) specimen had the PR of 91.8% (95% CI: 79.9%-103.7%), followed by rectal swabs; 87.8% (95% CI: 78.6%-96.9%) then sputum; 68.1% (95% CI: 56.9%-79.4%). A low PR was observed in oropharyngeal swabs; 7.6% (95% CI: 5.7%-9.6%) and blood samples; 1.0% (95% CI: -0.1%-2.1%) whereas no SARS-CoV-2 was detected in urine samples. Feces had a PR of 32.8% (95% CI:1 5.8%-49.8%). Nasopharyngeal swab, a widely used specimen had a PR of 45.5% (95% CI: 31.2%-59.7%). In this study, SARS-CoV-2 was highly detected in LRT specimens while no virus was detected in urinogenital specimens. BLF had the highest PR followed by rectal swab then sputum. Nasopharyngeal swab which is widely used had moderate PR. Low PR was recorded in oropharyngeal swab and blood samples while no virus was found in urine samples. Last, the virus was detected in feces, suggesting SARS-CoV-2 transmission by the fecal route.

Possible vertical transmission and antibodies against SARS-CoV-2 among infants born to mothers with COVID-19: A living systematic review.

Current evidence suggests that coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), is predominantly transmitted from human-to-human. However, evidence on vertical transmission and natural passive immunity among the newborns exposed to COVID-19 is scanty and varies. This poses a challenge on preventive interventions for the newborns. We conducted a systematic review to first, determine the likelihood of vertical transmission among COVID-19 exposed infants and second, determine whether antibodies against SARS-CoV-2 were generated among COVID-19 vertically exposed but negative infants. This review registered in PROSPERO searched evidence from PubMed/MEDLINE and Google Scholar, among others. About 517 studies were pooled, where 33 articles (5.8%) met the inclusion criteria such as infection prevention and control measures at birth. A total of 205 infants born to COVID-19 positive mothers were studied. Overall, 6.3% (13/205; 95% CI: 3.0%-9.7%) of the infants tested positive for COVID-19 virus at birth. Of 33 eligible studies, six studies (18.8%) reported about immunoglobulin G/M (IgG/IgM) against SARS-CoV-2. IgG/IgM were detected in 90% infants (10/11; 95% CI: 73.9%-107.9%) who tested negative for COVID-19 virus. The median antibody levels detected were 75.49 AU/ml (range, 7.25-140.32 AU/ml) and 3.79 AU/ml (range, 0.16-45.83 AU/ml), p = .0041 for IgG and IgM, respectively. In conclusion, the current evidence revealed a low possibility of vertical transmission of COVID-19 and antibodies against SARS-CoV-2 were detected among vertically exposed but negative infants. Further studies on transplacental transmission and the magnitude of natural passive immunity in infants born to mothers with COVID-19 are warranted.

Reliability of visual assessment of neonatal jaundice among neonates of black descent: a cross-sectional study from Tanzania.

BACKGROUND: Jaundice is common among neonates and if untreated can lead to kernicterus. Diagnosing neonatal jaundice (NJ) using Kramer's method (visual assessment) is considered user-friendly in resource-limited areas. However, there are conflicting findings on reliability of the Kramer's method in the diagnosis of NJ, particularly of black descent. Therefore, study aimed to determine the accuracy of Kramer's method in comparison to the total serum bilirubin (TSB) test in the diagnosis of NJ among neonates of black descent in Tanzania. METHODS: A cross-sectional study was conducted between June and July 2020 at Muhimbili National Hospital (MNH) in Dar es Salaam Tanzania. A total of 315 neonates were recruited consecutively. In each neonate, jaundice was assessed using Kramer's method and TSB test. NJ A total of 315 neonates were recruited i. A 2 X 2 table was created for the determination of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (+LR/-LR), and diagnostic accuracy (effectiveness) of Kramer's method. Cohen kappa (κ) was used to analyze the agreement between Kramer's method and TSB. Association between independent variables and presence of jaundice were assessed using the chi-square test and the p < 0.05 was considered to be statistically significant. RESULTS: The prevalence of NJ was 49.8% by Kramer's method and 63.5% by TSB. The Sensitivity, Specificity, PPV, and NPV of Kramer's method were 70.5, 86.1, 89.8, and 62.6%, respectively. The +LR and -LR were 5.07 and 0.34, respectively. The diagnostic accuracy of Kramer's method was 76.1%. There was a moderate agreement between Kramer's method and TSB results (κ = 0.524, P<0.001). No significant relationship was observed between the independent variables and the presence of NJ. CONCLUSION: Kramer has a good positive predictive value. However, due to low sensitivity and NPV one cannot say that overall predictive ability is good. Also, clinical assessment by Kramer's method should not be used for screening of NJ. Further studies are needed to investigate the utility of other non-invasive techniques in detecting NJ among neonates of black descent.

COVID-19 Pandemic: The Influence of Culture and Lessons for Collaborative Activities.

The rapid epidemiological shift from an epidemic/outbreak in Wuhan, China, to a global pandemic of COVID-19 in less than 3 months came with lessons the world's health system should learn to prepare for the future outbreaks. Since February 20, 2020, the total number of confirmed cases of COVID-19 has been increased very slowly in the countries of East Asia, including Japan, South Korea, and China, when compared with those in the Western countries. This chapter begins with an overview of the impact of COVID-19 on healthcare workers and public health facilities, followed by immediate global actions and research in response to the newly emerged pandemic. It includes an evaluation of the potential influence of culture on the implementation of different protective measures to combat the COVID-19 pandemic while at the same time offering suggestions that will make it easier for all populations to adapt protective steps against COVID-19 and other respiratory infectious diseases. Finally, the chapter provides a detailed discussion of lessons we have learned from the pandemic, leading to the conclusion that the transition from individualism to collaborative efforts is the treatment of universal pandemics.

Occurrence of septuple and elevated Pfdhfr-Pfdhps quintuple mutations in a general population threatens the use of sulfadoxine-pyrimethamine for malaria prevention during pregnancy in eastern-coast of Tanzania.

BACKGROUND: Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations compromise the effectiveness of sulfadoxine-pyrimethamine (SP) for treatment of uncomplicated malaria, and are likely to impair the efficiency of intermittent preventive treatment during pregnancy (IPTp). This study was conducted to determine the level of Pfdhfr-Pfdhps mutations, a decade since SP was limited for IPTp use in pregnant women in Tanzania. METHODS: P. falciparum genomic DNA was extracted from dried blood spots prepared from a finger prick. Extracted DNA were sequenced using a single MiSeq lane by combining all PCR products. Genotyping of Pfdhfr and Pfdhps mutations were done using bcftools whereas custom scripts were used to filter and translate genotypes into SP resistance haplotypes. RESULTS: The Pfdhfr was analyzed from 445 samples, the wild type (WT) Pfdhfr haplotype NCSI was detected in 6 (1.3%) samples. Triple PfdhfrIRNI (mutations are bolded and underlined) haplotype was dominant, contributing to 84% (number [n] = 374) of haplotypes while 446 samples were studied for Pfdhps, WT for Pfdhps (SAKAA) was found in 6.7% (n = 30) in samples. Double Pfdhps haplotype (SGEAA) accounted for 83% of all mutations at Pfdhps gene. Of 447 Pfdhfr-Pfdhps combined genotypes, only 0.9% (n = 4) samples contained WT gene (SAKAA-NCSI). Quintuple (five) mutations, SGEAA-IRNI accounted for 71.4% (n = 319) whereas 0.2% (n = 1) had septuple (seven) mutations (AGKGS-IRNI). The overall prevalence of Pfdhfr K540E was 90.4% (n = 396) while Pfdhps A581G was 1.1% (n = 5). CONCLUSIONS: This study found high prevalence of Pfdhfr-Pfdhps quintuple and presence of septuple mutations. Mutations at Pfdhfr K540E and Pfdhps A581G, major predictors for IPTp-SP failure were within the recommended WHO range. Abandonment of IPTp-SP is recommended in settings where the Pfdhfr K540E prevalence is > 95% and Pfdhps A581G is > 10% as SP is likely to be not effective. Nonetheless, saturation in Pfdhfr and Pfdhps haplotypes is alarming, a search for alternative antimalarial drug for IPTp in the study area is recommended.

Seroprevalence of Brucella infection and associated factors among pregnant women receiving antenatal care around human, wildlife and livestock interface in Ngorongoro ecosystem, Northern Tanzania. A cross-sectional study.

BACKGROUND: Brucellosis is a zoonotic disease transmitted to humans through contact with infected animals, animal products or consumption of infected dairy products. Brucella infection during pregnancy is of special interest due to association with adverse pregnancy outcomes. This study determined the seroprevalence and factors associated with Brucella infection among pregnant women around the human-wildlife-livestock interface area in Ngorongoro ecosystem, Northern Tanzania. METHODS: A facility-based cross-sectional study was conducted between May and June 2018 at six health facilities that provide antenatal services. Pregnant women receiving antenatal care were invited to participate. A structured questionnaire was used to collect socio-demographic and obstetric characteristics in addition to behavior and practices related to the occurrence of human brucellosis. The presence of serum immunoglobulin against Brucella was determined using Rose Bengal Plate Test (RBPT). The positive samples were further assayed for the presence of IgG and IgM using The enzyme-linkedimmunosorbent assay. Bivariate analysis was conducted to determine the variables associated with Brucella seropositivity. Multivariable logistic regression analysis was performed to examine the factors independently associations with Brucella seropositivity after adjustment for other explanatory variables. RESULTS: A total of 313 participants were enrolled in the study. The overall seroprevalence of Brucella infection was 10.9% (34/313) determined by Rose Bengal plate test. Of 34 positive individuals, 27(79.4%) and 8(23.5%) were positive in the ELISA specific for IgG and IgM Brucella antibodies respectively. Regular contact with manure (AOR 3.16, 95%CI 1.27-7.83) and preference for animal fresh milk (AOR 3.80, 95% CI 1.23-11.69), raw meat (AOR 2.58, 95% CI 1.14-5.81) and raw animal blood (AOR 2.71, 95% CI 1.15-6.35) increased the odds of being Brucella seropositive. Contact with the animal placenta were not associated with Brucella seropositivity after adjustment. CONCLUSION: This study has found that brucellosis is an important public health problem among pregnant women in areas with interactions of humans; livestock and wildlife. The risk of infection increased with the regular contact with manure and preference of raw foodstuffs like animal blood, meat, and milk. We emphasize the need for interventional strategies to reduce the risk of exposure.

Immunoglobulin G responses against falciparum malaria specific antigens are higher in children with homozygous sickle cell trait than those with normal hemoglobin.

BACKGROUND: High Immunoglobulin G (IgG) response to Plasmodium falciparum antigens is associated with partial malaria protection in sickle hemoglobin (HbS) children. However, this response has been more studied in children with heterozygous sickle cell trait (HbAS) but little explored in those with homozygous sickle cell trait (HbSS). The current study was conducted to determine the IgG responses against specific Plasmodium falciparum antigens in children with homozygous sickle cell trait (HbSS) by comparing to those with normal hemoglobin (HbAA). METHODS: A cross sectional study was conducted between April and July 2018 in Dar es Salaam tertiary hospitals. Parents were consented for their child to give about 5 ml of venous blood. IgG concentration from the blood plasma of 220 children (110 HbAA vs. 110 HbSS) were determined using indirect Enzyme Linked Immunosorbent Assay (ELISA). Then IgG medians were compared between the groups with prism 5 software (GraphPad) using Mann Whitney U test. Where the differences in age, hemoglobin levels and body weight between the groups was analyzed using independent sample t test. Multiple linear regressions were used to control cofounding variables such as body weight, age and hemoglobin level using statistical package for social sciences software (SPSS version 23). P value <0.05 was considered statistically significant. RESULTS: The median IgG concentration to PfEBA-175, Pfg27, yPfs28C antigens were HbSS; 20.7 ng/ml (IQR; 18.1-25.6) vs. HbAA; 2.3 ng/ml (IQR; 1.21-3.04), HbSS; 2.76 ng/ml (IQR: 2.08-5.69) vs. HbAA; 1.36 ng/ml (IQR: 1.28-1.76), and HbSS; 26,592 ng/ml (IQR: 10817-41,462) vs. HbAA; 14,164 ng/ml (IQR; 3069-24,302) respectively (p < 0.0001 for all IgG). In both groups; age, body weight and hemoglobin level had no impact on the levels of IgG responses to Plasmodium falciparum antigens except for HbAA group which showed a significant increase in IgG against Pfg27 by 0.004 ng/ml with 1 g/dl increase in Hb level (p = 0.028). CONCLUSIONS: This study found significant higher levels of specific Plasmodium falciparum IgG responses in children with homozygous sickle cell trait than those with normal hemoglobin.

Diagnostic performance of CareStart™ malaria HRP2/pLDH test in comparison with standard microscopy for detection of uncomplicated malaria infection among symptomatic patients, Eastern Coast of Tanzania.

BACKGROUND: CareStart™ malaria HRP2/pLDH (Pf/pan) combo test is one of the several rapid diagnostic tests (RDT) approved for diagnosis of malaria at the point of care in Tanzania. However, there are limited studies on the diagnostic performance of RDT after wide scale use in primary health care facilities in Tanzania. Therefore, this study was carried out to determine the diagnostic performance of RDT when compared with blood smear (BS) microscopy as a reference standard. METHODS: A cross-sectional study was conducted between March and August 2019 at Kibiti Health Centre, Pwani region, Tanzania. Blood samples for malaria tests were collected from patients with malaria symptoms. Diagnostic performance parameters of RDT, i.e. sensitivity, specificity, positive and negative likelihood ratios (LR+/-), diagnostic accuracy and predictive values were determined using contingency table. An agreement between RDT and microscopy was statistically determined by Cohen's kappa test. RESULTS: Of 980 patients screened, 567 (57.9%) were found to be malaria positive by RDT, whereas 510 patients (52%) were positive by microscopy. Of the 510 microscopy-positive patients, 487 (95.5%) were infected with Plasmodium falciparum. The geometric mean parasite density was 2921parasites/µl, whereas majority (68.6%) of patients had parasite density greater than 10,000/µl. The sensitivity, specificity, positive and negative predictive values of CareStart™ were 99.8%, 87.6%, 89.8%, and 99.8%, respectively. The LR+ and LR- were 8.0 and 0.002, respectively. The diagnostic accuracy was 0.5. There was a strong agreement between the results obtained using CareStart™ and BS microscopy (kappa = 0.863, P < 0.0001). CONCLUSION: CareStart™ malaria HRP2/pLDH (Pf/pan) had high sensitivity and strong agreement with microscopy results. However, moderate specificity of RDT resulted in a substantial number of patients with false positive malaria test. Wherever available, microscopy should be used to confirm RDT test results.

Utilization patterns of malaria chemoprophylaxis among Tanzanian children attending sickle cell clinic in Dar es Salaam tertiary hospitals.

BACKGROUND: Malaria is among the leading cause of infection in individuals with sickle cell disease (SCD) living in sub-Saharan Africa, including Tanzania. However, after 2005 the standard treatment guidelines (STGs) on malaria chemoprevention for SCD patients were non-existent, and at present no medicine is recommended for SCD patients. Since several anti-malarials have been approved for the treatment of malaria in Tanzania, it is important to establish if there is a continued use of chemoprevention against malaria among SCD children. METHODS: A cross-sectional, hospital-based study was conducted between January and June 2019 at tertiary hospitals in Dar es Salaam. Data were collected using a semi-questionnaire and analysed using SPSS software version 25. The descriptive statistics were summarized using proportions, while factors associated with the use of chemoprophylaxis were analysed using multivariate logistic regression. Statistical significance of p < 0.05 was accepted. RESULTS: A total of 270 SCD children were involved. The median age of SCD children was 6 years (interquartile range (IQR): 3-11 years). Of 270 SCD children, 77% (number (n) = 218) of children with SCD had not been diagnosed with malaria in the previous year, whereas 12.6% (n = 34) of children were admitted because of malaria in the previous year. Regarding the use of chemoprophylaxis in SCD children, 32.6% (n = 88) of parents were aware that, chemoprophylaxis against malaria is recommended in SCD children. Of the 270 participants, 17% (n = 46) were using malaria chemoprophylaxis. A majority used artemisinin combination therapy (ACT), 56.8% (n = 26). Of 223 parents who did not give chemoprophylaxis, the majority (n = 142, 63.7%) indicated unavailability at clinics as the reason. Children whose parents were primary level educated were 9.9 times more likely to not use chemoprophylaxis (adjusted odds ratio (AOR); 9.9, 95% CI 1.8-56.5, P = 0.01) compared to those whose parents had tertiary education. CONCLUSION: Despite the lack of STGs, a small proportion of children with SCD were using malaria chemoprophylaxis where the majority used ACT, i.e., dihydroartemisinin-piperaquine.

C - reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania.

BACKGROUND: Chronic inflammation has been associated with dysglycemia among people living with HIV (PLHIV). There is however, limited data regarding this phenomenon in sub-Sahara Africa (SSA). Therefore we assessed the levels of C-reactive protein (CRP) and Interleukin 6 (IL-6) on a cohort of PLHIV and its associations with dysglycemia in Tanzania. METHODS: We conducted a cross-sectional study at the Infectious Disease Clinic (IDC) in Tanzania from March to May 2018. Purposive sampling was used to identify participants who had an undetectable viral load, were on 1st line anti-retroviral therapy (ART) and had an overnight fast. The WHO stepwise approach for non-communicable disease (NCD) surveillance was used to collect data. Fasting blood glucose and blood glucose after 75 g oral glucose load was measured, and Enzyme-linked immunosorbent assay (ELISA) was used to test for inflammatory markers (IL-6 and CRP). Associations were explored using the Chi square test and binary logistic regression was performed to estimate the odds ratios. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 240 participants were enrolled. Forty two percent were overweight/obese (> 25 kg/m2), 89% had a high waist to height ratio. The median ART duration was 8(5-10) years. The prevalence of dysglycemia among our cohort of PLHIV was 32%. High CRP was associated with a 2.05 increased odds of having dysglycemia OR 2.05 (1.15-3.65) (p = 0.01). Taking stavudine was associated with a 1.99 odds of having dysglycemia OR 1.99 (1.04-3.82) (p = 0.03).We did not find a significant association between IL-6 and dysglycemia. CONCLUSION: High CRP and taking stavudine were significantly associated with dysglycemia among PLHIV with undetectable viral load.

Implementation research for promoting access and rational use of antibiotics for children: lessons learnt from Tanzania.

Implementation research (IR) has proved to be a potential catalyst in facilitating the uptake of evidence-based innovations into routine practices and thereby maximizing public health outcomes. IR not only focuses on the effectiveness of the innovations but also identifies and addresses the barriers and facilitators to maximize their uptake into routine practices. This article describes the processes undertaken to implement a research project aimed at promoting access and rational use of antibiotics for children (PARAC). It also provides an overview of the lessons learnt during its implementation in Tanzanian hospital and community settings.

WHO/INRUD prescribing indicators among tertiary regional referral hospitals in Dar es Salaam, Tanzania: a call to strengthen antibiotic stewardship programmes.

Background: Antibiotic prescribing should be guided by national essential medicines lists (NEMLs) and treatment guidelines; however, there are inadequate data on antibiotic utilization patterns in tertiary hospitals in Tanzania. This study aimed to determine antibiotic prescribing patterns in tertiary hospitals in Dar es Salaam, Tanzania. Methods: A retrospective cross-sectional study was conducted in three regional referral hospitals. About 200 prescription records from 2020 to 2022 were analysed at each hospital for prescribing patterns using WHO/ International Network of Rational Use of Drugs (INRUD) indicators (1993) and the AWaRe 2021 classification. Factors associated with receiving an antibiotic prescription were assessed using a logistic regression model. Facilities were ranked on prescribing practices using the index of rational drug prescribing (IRDP). Results: A total of 2239 drugs were prescribed, of which 920 (41.1%) were antibiotics. An average of 3.7 ±â€Š1.5 (optimal: 1.6-1.8) total medicines and 1.53 ±â€Š0.78 antibiotics were prescribed per patient. About 88.0% (528) of the prescriptions contained antibiotics (optimal: 20.0%-26.8%), while 78.2% (413) of all antibiotic prescriptions contained injections (optimal: 13.4%-24.1%). Furthermore, 87.5% (462) of the antibiotics were prescribed in generic names (optimal: 100%), while 98.7% (521) conformed to the NEML (optimal: 100%). Metronidazole was the most frequently prescribed antibiotic (39.2%; n = 134), followed by ceftriaxone (37.1%, n = 127) and amoxicillin/clavulanic acid (8.5%, n = 29). Conclusions: We found substantial empirical prescribing and overuse of antibiotics exceeding WHO recommendations. Antibiotic overuse varied across the hospitals. Being male, having underlying conditions such as diabetes mellitus, and/or being treated at Temeke hospital were associated with receiving an antibiotic prescription. We recommend strengthening antibiotic stewardship programmes in the studied facilities.

High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam.

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ([Formula: see text] standard deviation) was 44.0 ([Formula: see text] 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9-10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34-96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area.

Microbiological Quality of Selected Local and Imported Non-Sterile Pharmaceutical Products in Dar es Salaam, Tanzania.

Background: Pathogenic and non-pathogenic microbial contaminants can cause physical-chemical alterations of pharmaceuticals and medicine-related infections. This study aimed to examine the microbiological quality of selected local and imported non-sterile pharmaceutical products in the Dar es Salaam market and the antibiogram of the isolated microorganisms. Methods: Samples were collected between April and June 2021 and analysed for microbial content as per the harmonised methods of the European Pharmacopoeia (EP). Antibiotic susceptibility of the microbial isolates was studied using Kirby-Bauer disc diffusion method. Results: Fifty percent (50%) of the samples failed both bacterial and fungal enumeration tests. In this study, local products recorded lower microbial counts than imported products. Major bacterial contaminants isolated were P. aeruginosa (45.5%), S. epidermidis, (45.5%) and K. pneumoniae, while major fungal contaminants were A. flavus (58.3%), followed by A. fumigatus (25%) and Penicillium spp (16.7%). The isolated bacterial contaminants recorded high resistance levels to commonly used antibiotics. Conclusion: The tested products were contaminated with microorganisms at different levels, most of them exceeding the maximum acceptable colony counts. Syrups or suspensions were more contaminated than tablets and capsules. The isolated bacterial contaminants were highly resistant to commonly used antibiotics. Recommendations: We recommend that pharmaceutical manufacturers abide by good manufacturing, distribution and storage practices to limit contamination and cross-contamination of products. Responsible drug regulatory authorities should heighten the frequency of inspection of manufacturing facilities and regularly conduct post-marketing surveillance (PMS) of registered products to assess continued conformity to GMP guidelines. Future studies should involve samples collected directly from manufacturing sites.

Isolation Frequency of Fluconazole-Resistant Candida Species From Cockroaches: A Cross-Sectional Study From a National Hospital in Dar es Salaam, Tanzania.

BACKGROUND: Cockroaches are common pests in homes and hospitals. They cause allergic reactions in some individuals and are potential vectors for various infectious pathogens. The study investigated the extent to which hospital cockroaches act as vectors and reservoirs of medically important fungal pathogens on their external surfaces. METHODS: Cockroaches were captured from the selected hospital locations including the burn unit, adult surgical wards, pediatric oncology wards, intern hostel kitchen, and the central kitchen of a national referral teaching hospital in Tanzania. Normal saline washings from the external surface of cockroaches were cultured on standard mycological media to facilitate isolation and identification of medically important molds and yeasts. The susceptibility of Candida species isolates to fluconazole was tested using the Clinical and Laboratory Standards Institute (CLSI) M27-A3 microdilution method. RESULTS: A total of 69 cockroaches were captured from various hospital sites between February and April 2017. All cockroaches captured were shown to carry medically important fungi. A total of 956 medically important fungi were isolated; 554 (57.9%) were of Candida species, 222 (23.2%) were of Aspergillus species, 30 (3.1%) were of​​​​​​​ Cladosporium species, 17 (1.8%) were of​​​​​​​ Rhizopus species, 11 (1.2%) were of​​​​​​​ Geotrichum species, nine (0.9%) were of​​​​​​​ Penicillium species, seven (0.7%) were of​​​​​​​ Alternaria species, six (0.6%) were of​​​​​​​ Fusarium species, three (0.3%) were of​​​​​​​ Mucor species, and 97 (10.1%) were of other species. Of the Aspergillus species, Aspergillus fumigatus (111, 50.0%) was the most commonly isolated, followed by Aspergillus niger (35, 15.8%) among the Aspergillus isolates. Out of the 103 selected isolates, 18 (17.5%) of the Candida isolates normally not intrinsically resistant to fluconazole demonstrated resistance to this drug. Resistance was most frequently found in Candida parapsilosis (3, 30%), Candida pseudotropicalis (10, 23.8%), and Candida glabrata (2, 18.2%). The isolates with the least proportion of resistance to fluconazole were Candida albicans (2, 6.3%). CONCLUSION: Cockroaches from this hospital may act as reservoirs of medically important opportunistic fungi exhibiting resistance to fluconazole.