Antenatal corticosteroid therapy, delivery intervals and perinatal mortality in low-resource settings.

BACKGROUND: Uncertainty exists regarding the ideal interval between the administration of antenatal corticosteroids (ACS) and delivery. The study's objective was to assess the risks of perinatal mortality and respiratory distress syndrome (RDS) among preterm neonates whose mothers gave birth within 48 h of the administration of ACS and those whose mothers gave birth between 48 h and 7 days. METHODS: The study design was a secondary analysis of data from an observational prospective chart review study that was carried out in Tanzania in 2020. Preterm infants born to mothers who got at least one dose of ACS between 28 and 34 weeks of pregnancy were included. RESULTS: A total of 346 preterm neonates (294 singletons and 52 twins) were exposed to ACS. Compared to infants born 48 h following the first dose of ACS, those exposed to the drug between 48 h and 7 days had significantly decreased rates of perinatal mortality and RDS. Multivariable analysis revealed that infants exposed ACS between 48 h and 7 days prior to delivery had lower risk of perinatal mortality (aRR 0.30, 95% CI 0.14-0.66) and RDS (aRR 0.27, 95% CI 0.14-0.52). CONCLUSION: The first dose of ACS given between 48 h and 7 days before delivery was associated with a lower risk of perinatal mortality and RDS than when the first dose was given <48 h before delivery. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.

Preterm infants exposed to antenatal corticosteroids (ACS) have lower rates of perinatal mortality and morbidity. Uncertainty exists regarding the ideal interval between the administration of ACS and delivery. We conducted a secondary analysis of data from a study that included preterm infants born in four hospitals in Tanzania. We investigated whether there were differences in perinatal mortality and respiratory distress syndrome between preterm neonates whose mothers delivered within 48 h of receiving a partial course of ACS and those whose mothers delivered between 48 h and 7 days after a full course of ACS therapy. Participants were the preterm infants of women who received ACS between 28 and 34 weeks of gestation. Neonates exposed to ACS between 48 h and 7 days prior to delivery had significantly lower risks of perinatal mortality and respiratory distress syndrome compared to infants who were delivered <48 h after ACS administration. This finding highlights the importance of optimizing the timing of ACS administration to maximize its potential benefits and minimize risks to preterm neonates. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.

Assessment of snakebite management practices at Meserani Juu in Monduli District, Northern Tanzania.

BACKGROUND: Snakebite envenoming represents a tragically neglected tropical disease mostly affecting poor people living in remote areas of developing countries, primarily in sub-Saharan Africa. Anti-snake venom (ASV) is the only approved specific treatment for systemic envenoming from snakebite, but it remains largely unavailable in many parts of developing countries. There is paucity of data on snakebite management practice in Tanzania. This study aimed at assessing the community management practices of snakebite and availability of anti-snake venom in the public health facilities in Monduli District, Northern Tanzania. METHODS: A cross sectional study was carried out between May and June, 2018 involving 67 victims, 147 other household members, and 35 public health facilities. A structured questionnaire, respondent interview, and health facility report/document review were considered during data collection. Clean data were analyzed using SPSS version 20. RESULTS: Sixty-seven snakebite victims and 147 other household members were interviewed during a household survey. All snakebite cases reported to having visited a health facility after snakebite with the majority 55/67 (82.1%) reporting the use, prior attendance to medical care, of some form of local treatment such as tourniquets 13 (19.4%), local incision 11 (16.4%), and snakestone 7 (10.4%). None of the public health facilities in Monduli District attended a snakebite case and had never stocked anti-snake venom products. In this area, 45 snakebite cases were reported to be managed at Meserani snake park clinic where anti-snake venom products were available and provided for free in the period between January 2017 and December 2017. CONCLUSION: Majority of the snakebite cases at Meserani Juu relied on local methods for the management of snake bites of which most are of unknown efficacy and safety. Furthermore, none of the primary public health facilities in Monduli District stocked antivenom despite being a habitat for different kinds of venomous snakes. The government and local non-government organizations should collaborate so as to improve the anti-snake venom availability and the provision of snakebite preventive and management awareness programs, especially to the rural communities.

Association between antenatal corticosteroids use and perinatal mortality among preterm singletons and twins in Mwanza, Tanzania: an observational study.

OBJECTIVES: To examine the association between antenatal corticosteroids (ACS) use and perinatal mortality in singletons and twins delivered before 35 weeks of gestation. DESIGN: Secondary analysis of data from an observational prospective chart review study that investigated if exposure to ACS was associated with lower rates of perinatal mortality in preterm infants. SETTING: This study was conducted in four hospitals located in Mwanza region, Tanzania. PARTICIPANTS: The study population included all preterm singletons and twins delivered at these hospitals between 24 weeks 0 days and 34 weeks 6 days of gestation from July 2019 to February 2020. OUTCOME MEASURES: The primary outcome was perinatal mortality; the secondary outcome was respiratory distress syndrome (RDS). RESULTS: The study included 844 singletons and 210 twin infants. Three hundred and fourteen singletons (37.2%) and 52 twins (24.8%) were exposed to at least one dose of ACS. Adjusted multivariate analyses revealed that among singletons' exposure to ACS was significantly associated with a lower likelihood of perinatal mortality, adjusted relative risk (aRR) 0.30 (95% CI 0.22 to 0.40) and RDS, aRR 0.92 (95% CI 0.87 to 0.97). In twin infants, exposure to ACS was associated with a reduced risk of RDS only, aRR 0.87 (95% CI 0.78 to 0.98). CONCLUSION: The use of ACS between 24 weeks 0 days and 34 weeks 6 days of gestation in both singletons and twins in low-resource settings is associated with positive infant outcomes. No adverse effects were noted. Further research that examines the benefits of ACS for twin infants is needed.

Limited care offered to people with epilepsy in Mwanza, Tanzania: need for intervention.

INTRODUCTION: epilepsy is a very common neurological disorder which is associated with high socioeconomic burden. While up to 90% of people with epilepsy (PWE) in developing countries do not get appropriate treatment, there is limited information about care offered to PWE in Tanzania. This study aimed to describe available care offered to PWE in Mwanza. METHODS: a cross-sectional study involving health care workers (HCWs) and PWE attending five selected hospitals outpatient clinics of Mwanza region was done. HCWs completed self-administered questionnaires while PWE or caretakers were interviewed using structured questionnaires. Coded data were analyzed using SPSS. RESULTS: a total of 18 HCWs and 218 PWE (or their care takers) participated in this study. Health care workers rarely used investigations to confirm epilepsy diagnosis or explore its causes. 10/18 (55.6%) of HCWs reported that counseling was given to patients but counseling information was largely inadequate regarding the use of anti-epileptic drugs (AEDs). The AEDs prescriptions were dictated by drug availability and affordability to patients. Among 197 PWE, whose AEDs doses were revealed, 136 (69.0%) were under-medicated. No follow-up investigation was done to all PWE who were interviewed. There was discrepancy between hospitals and practitioners regarding withdrawal of AEDs. CONCLUSION: people with epilepsy in Mwanza received limited care. Patients were not thoroughly investigated, counseled and followed-up, and had limited choice and accessibility to AEDs. Some patients particularly in district hospitals were under-medicated despite of seizure recurrence. We recommend short-course training about epilepsy management to the HCWs who diagnose and treat PWE regularly.

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. METHODS: Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/µl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/µl. RESULTS: No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/µl compared to -37.42 ± 10.77 cells/µl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. CONCLUSIONS: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01299948.

Plasma concentrations of efavirenz and nevirapine among HIV-infected patients with immunological failure attending a tertiary hospital in North-western Tanzania.

BACKGROUND: Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. MATERIALS AND METHODS: A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. RESULTS: Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations. CONCLUSION: There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure.

Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania.

BACKGROUND: Drug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs. METHODS: A prospective single cohort study was conducted at Igombe health centre using artemether-lumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously. RESULTS: A total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/µl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites. CONCLUSION: The efficacy of artemether-lumefantrine for treatment of uncomplicated malaria is still high in the study area although the rate of re-infection is higher than previously reported. Parasite clearance after 48 hours was lower compared to previous studies. The prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study area while markers for SP resistance is still high. Artemether-lumefantrine may be selecting for wild type alleles on both positions (437 and 540) of pfdhps.

Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda-a reflection of differences in policies regarding withdrawal of chloroquine?

BACKGROUND: Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine-pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women. METHODS: Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products. RESULTS: The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates. CONCLUSIONS: The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down.

HIV drug resistance (HIVDR) in antiretroviral therapy-naïve patients in Tanzania not eligible for WHO threshold HIVDR survey is dramatically high.

BACKGROUND: The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population. METHODS AND FINDINGS: HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25-63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072-0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095-0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. CONCLUSIONS: ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.