Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018.

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2019.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a major contributor to the substantial reductions in global malaria morbidity and mortality over the last decade. In Tanzania, artemether-lumefantrine (AL) was introduced as the first-line treatment for uncomplicated Plasmodium falciparum malaria in 2006. The World Health Organization (WHO) recommends regular assessment and monitoring of the efficacy of the first-line treatment, specifically considering that artemisinin resistance has been confirmed in the Greater Mekong sub-region. This study's main aim was to assess the efficacy and safety of AL for treating uncomplicated P. falciparum malaria in Tanzania. METHODS: This was a single-arm prospective antimalarial drug efficacy trial conducted in four of the eight National Malaria Control Programme (NMCP) sentinel sites in 2019. The trial was carried out in outpatient health facilities in Karume-Mwanza region, Ipinda-Mbeya region, Simbo-Tabora region, and Nagaga-Mtwara region. Children aged six months to 10 years with microscopy confirmed uncomplicated P. falciparum malaria who met the inclusion criteria were recruited based on the WHO protocol. The children received AL (a 6-dose regimen of AL twice daily for three days). Clinical and parasitological parameters were monitored during follow-up over 28 days to evaluate drug efficacy. RESULTS: A total of 628 children were screened for uncomplicated malaria, and 349 (55.6%) were enrolled between May and September 2019. Of the enrolled children, 343 (98.3%) completed the 28-day follow-up or attained the treatment outcomes. There were no early treatment failures; recurrent infections during follow-up were common at two sites (Karume 29.5%; Simbo 18.2%). PCR-corrected adequate clinical and parasitological response (ACPR) by survival analysis to AL on day 28 of follow-up varied from 97.7% at Karume to 100% at Ipinda and Nagaga sites. The commonly reported adverse events were cough, skin pallor, and abdominal pain. The drug was well tolerated, and no serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria in Tanzania in 2019. The high recurrent infections were mainly due to new infections, highlighting the potential role of introducing alternative artemisinin-based combinations that offer improved post-treatment prophylaxis, such as artesunate-amodiaquine (ASAQ).

Sexual and reproductive health among men with genital schistosomiasis in southern Tanzania: A descriptive study.

Male genital schistosomiasis (MGS) is a significantly neglected condition, and its consequences often receive inadequate attention. The disease is suggested to cause schistosomiasis-induced sexual and reproductive health problems among males. The study was conducted to investigate the prevalence of MGS, sexual and reproductive health problems that could be caused by MGS among adult males in Mtama district. A community-based cross-sectional study using quantitative methods was carried out among males aged ≥ 18 years in selected households. Semen and urine samples were collected from each participant to establish the prevalence of MGS and urogenital schistosomiasis respectively. Semen quality was macroscopically and microscopically assessed. Urine samples were analyzed using filtration technique. A structured questionnaire interview was carried out to collect socio-demographic data, sexual and reproductive health information. Descriptive statistics were used to provide a summary of each variable. The prevalence (proportions) were presented in percentages and their respective 95% confidence intervals. A total of 223 adult males participated in this study. The prevalence of MGS and urogenital schistosomiasis were 5.8% (95% CI; 3.1%-9.0%) and 22.4% (95% CI; 16.6%-27.8%) respectively. The prevalence of Schistosoma haematobium eggs in semen was found high among young adults 12/129 (9.3%, 95% CI; 4.9%-15.7%), who never attended to school 6/35 (17.1%, 95% CI; 6.6%-33.6%), petty traders 4/26 (15.4%, 95% CI; 4.4%-34.9%), never impregnated woman 9/70 (12.9%, 95% CI: 6.6%-33.6%), experienced pain during ejaculation 4/17 (23.5%, 95% CI; 4.9%-15.7%), and with brownish semen 2/5 (40%, 95% CI; 4.9%-15.7%). According to the findings, MGS, like urogenital schistosomiasis, is prevalent in southern Tanzania. The disease is prevalent among males with some reproductive and sexual issues. This highlight the need for more research to investigate the association of MGS and male reproductive and sexual health for improved health services among males.

Efficacy of artesunate-amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria in mainland Tanzania.

BACKGROUND: Diversification of artemisinin-based combination therapy (ACT) is suggested as one of the strategies that can be used to contain artemisinin resistance. Artesunate-amodiaquine (ASAQ) is one of the artemisinin-based combinations that can be used in the diversification strategy as an alternative first-line treatment for uncomplicated malaria in mainland Tanzania. There is however limited data on the efficacy of ASAQ in mainland Tanzania. This study assessed the efficacy of ASAQ for treatment of uncomplicated Plasmodium falciparum malaria in selected sentinel sites for therapeutic efficacy studies in mainland Tanzania. METHODS: Between December 2018 and March 2020, children aged between 6 months and 10 years, attending at Nagaga, Mkuzi, and Mlimba primary health facilities, and with suspected uncomplicated malaria infection were screened for eligibility to participate in the study. Malaria infection was screened using microscopy. Children with uncomplicated P. falciparum monoinfection and who fulfilled all other inclusion criteria, and had none of the exclusion criteria, according to the World Health Organization (WHO) guidelines, were treated with ASAQ. Follow-up visits were scheduled on days 0, 1, 2, 3, 7, 14, 21, and 28 or on any day of recurrent infection for clinical and laboratory assessment. Polymerase chain reaction (PCR)-corrected cure rate on day 28 was the primary outcome. RESULTS: A total of 264 children, 88 in each of the three study sites (Mlimba, Mkuzi and Nagaga health facilities) were enrolled and treated with ASAQ. The ASAQ PCR-corrected cure rate was 100% at all the three study sites. None of the participants had early treatment failure or late clinical failure. Furthermore, none of the participants had a serious adverse event. CONCLUSION: ASAQ was highly efficacious for the treatment of uncomplicated P. falciparum malaria in mainland Tanzania, therefore, it can be deployed as an alternative first-line treatment for uncomplicated malaria as part of diversification strategy to contain the spread of partial artemisinin resistance in the country.

Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021.

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.

Accuracy and precision of dried urine spot method for the detection of Schistosoma mansoni circulating cathodic antigens in resource-limited settings.

BACKGROUND: The World Health Organization recommends the use of Schisto point-of-care circulating cathodic antigens (Schisto POC-CCA) for screening of Schistosoma mansoni as it offers better sensitivity than microscopy. However, there are limitation facing the use of this method including timely availability of the test cassettes. The aim of this study was to determine the reliability of dried urine spot (DUS) method for collection of urine and detection of S. mansoni using Schisto POC-CCA cassettes in a resource-limited settings. METHODS: A cross-sectional study was conducted between October and November 2022 among 250 primary school children in Sengerema District, northwestern Tanzania. S. mansoni CCA was detected in filter paper-based DUS, liquid urine using DUS Schisto POC-CCA (index), and direct urine Schisto POC-CCA (comparator) methods respectively. S. mansoni eggs in stool were detected using duplicate Kato-Katz (KK) method. The measures of accuracy were computed and compared between the index and comparator methods. The strength of agreement between inter-raters precisions was tested using Cohen's kappa (k). RESULTS: This study revealed S. mansoni prevalence rates of 28.8%, 54.0% and 50.8% by duplicate KK, direct urine Schisto POC-CCA and DUS Schisto POC-CCA methods respectively. The mean intensity of infection among infected participants was 86.3 eggs per gram of stool (EPG) ranging from 12.0 EPG to 824.0 EPG. The sensitivity of DUS Schisto POC-CCA and direct urine Schisto POC-CCA was 94.44% (95% CI: 89.15-99.74%) and 97.22% (95% CI: 93.43-100.00%) respectively. The DUS Schisto POC-CCA method had slightly higher specificity (66.85%) than direct urine Schisto POC-CCA method (63.48%). The accuracy of the DUS Schisto POC-CCA was found to be slightly high (74.80%, 95% CI: 68.94-79.06%) compared to that of direct urine Schisto POC-CCA (73.20%, 95% CI: 67.25-78.59%). There was good agreement between two laboratory technologists who performed the DUS Schisto POC-CCA method on similar samples (k = 0.80, 95% CI: 0.59-0.95). CONCLUSIONS: The DUS Schisto POC-CCA method had comparable S. mansoni detection accuracy to direct urine Schisto POC-CCA. This suggests that the method could be a potential alternative to direct urine Schisto POC-CCA for screening S. mansoni in resource-limited situations.

Dried urine spot method for detection of Schistosoma mansoni circulating cathodic antigen in resource-limited settings: a proof of concept study.

Background: Among the challenges in schistosomiasis surveillance and mapping surveys is the lack of a sensitive diagnostic method especially in low transmission setting. Currently, the WHO recommends the use point-of-care circulating cathodic antigen (Schisto POC-CCA) tests for surveillance and mapping of intestinal schistosomiasis. However, Schisto POC-CCA test has its drawbacks, one of which is the timely availability of test kits. One approach to overcoming this challenge is to develop a low-cost sampling method that allows for the collection and transport of urine specimens even in resource-limited settings. Objective: To develop a simple and efficient method for the collection and detection of Schistosoma mansoni (S. mansoni) CCA using urine spotted onto filter paper. Methodology: To develop a dried urine spot (DUS) method, various dried matrix extraction parameters were tested and optimized using predesigned steps. The parameters include the size of filter paper (determined by the number of punches), volume of solvents, and type of solvent. Moreover, we optimized the incubation conditions (time and temperature). Urine and stool specimens to conduct the experiments were collected from volunteer fishermen in Mwanza and this project staff. Data were entered into the Microsoft Excel spreadsheet and IBM Statistical Package for the Social Sciences, version 20 for analysis. Results: The optimal results were obtained when the procedure was run under the following conditions: Five punches of filter paper containing DUS were dissolved in 150 µl of distilled water and incubated at room temperature for 24 hours in an Eppendorf tube. More than 93% of the assays performed under these conditions produced results that were either comparable to or significantly better than the standard method. Conclusion: This study demonstrates the feasibility of collecting urine specimen (DUS) using filter paper and detecting Schistosoma CCA from DUS specimen using the Schisto POC-CCA cassette test.

Burden and factors associated with ongoing transmission of soil-transmitted helminths infections among the adult population: A community-based cross-sectional survey in Muleba district, Tanzania.

BACKGROUND: In Tanzania, school-based Mass Drug Administration (MDA) campaigns have been the main strategy for the prevention and control of Soil Transmitted Helminths (STH) infection. Adults are not part of the program and could remain as the reservoir of infection, favoring continuity in transmission. Water, Sanitation, and Hygiene (WaSH) issues and slow progress in community awareness promotion campaigns contribute to the persistence of STH as public health issue among target populations notwithstanding the achievements of the control interventions. OBJECTIVE: This study aimed to determine the current prevalence and the risk factors associated with ongoing transmission of STH infection among adults in Muleba District, Tanzania. METHODOLOGY: A household-based quantitative cross-sectional study was carried out among 552 adults in Muleba district. Through a quantitative interviewer-administered questionnaire, information was registered related to socio-demographic characteristics, level of knowledge on the disease, and WaSH factors. The prevalence of STH and estimation of its intensity were assessed by analyzing stool samples through formol-ether concentration and the Kato-Katz technique. Descriptive statistics was used to summarise data; logistic regression to determine the association between STH infection and socio-demographic and WaSH factors. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 552 adults were included in the study; 50.7% (280/552) were female. The median age was of 30 years, ranging from 18 to 73 years. A prevalence of 9.1% (50/552) for STH infection was reported; the prevalence of Hookworm Spp., Ascaris lumbricoides, and Trichuris trichiura was 7.43%, 0.91%, and 0.72%, respectively. The factors significantly associated with STH infection were farming (aOR = 3.34, 95% CI: 1.45-7.70), the habit of not wearing shoes in general (aOR = 5.11, 95% CI: 1.55-16.87), and during garden activities (aOR = 4.89, 95% CI: 1.47-16.28). CONCLUSIONS AND RECOMMENDATIONS: We observed an aggregated prevalence of STH infections (Ancylostoma duodenale, Trichuris trichiura, and Ascaris lumbricoides) of 9.1% among the adult population, indicating a decreasing prevalence but ongoing transmission. Integrated management is needed to address practices contributing to ongoing transmission.

Similar Prevalence of Plasmodium falciparum and Non-P. falciparum Malaria Infections among Schoolchildren, Tanzania1.

Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4 Plasmodium spp. by performing PCR on dried blood spots collected within 8 regions of Tanzania during 2017. Among 3,456 schoolchildren, 22% had P. falciparum, 24% had P. ovale spp., 4% had P. malariae, and 0.3% had P. vivax infections. Most (91%) schoolchildren with P. ovale infections had low parasite densities; 64% of P. ovale infections were single-species infections, and 35% of those were detected in low malaria endemic regions. P. malariae infections were predominantly (73%) co-infections with P. falciparum. P. vivax was detected mostly in northern and eastern regions. Co-infections with >1 non-P. falciparum species occurred in 43% of P. falciparum infections. A high prevalence of P. ovale infections exists among schoolchildren in Tanzania, underscoring the need for detection and treatment strategies that target non-P. falciparum species.

Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children.

BACKGROUND: Transmission of malaria in sub-Saharan Africa has become increasingly stratified following decades of malaria control interventions. The extent to which environmental and land cover risk factors for malaria may differ across distinct strata of transmission intensity is not well known and could provide actionable targets to maximize the success of malaria control efforts. METHODS: This study used cross-sectional malaria survey data from a nationally representative cohort of school-aged children in Tanzania, and satellite-derived measures for environmental features and land cover. Hierarchical logistic regression models were applied to evaluate associations between land cover and malaria prevalence within three distinct strata of transmission intensity: low and unstable, moderate and seasonal, and high and perennial. RESULTS: In areas with low malaria transmission, each 10-percentage point increase in cropland cover was associated with an increase in malaria prevalence odds of 2.44 (95% UI: 1.27, 5.11). However, at moderate and higher levels of transmission intensity, no association between cropland cover and malaria prevalence was detected. Small associations were observed between greater grassland cover and greater malaria prevalence in high intensity settings (prevalence odds ratio (POR): 1.10, 95% UI: 1.00, 1.21), and between greater forest cover and reduced malaria prevalence in low transmission areas (POR: 0.74, 95% UI: 0.51, 1.03), however the uncertainty intervals of both estimates included the null. CONCLUSIONS: The intensity of malaria transmission appears to modify relationships between land cover and malaria prevalence among school-aged children in Tanzania. In particular, greater cropland cover was positively associated with increased malaria prevalence in areas with low transmission intensity and presents an actionable target for environmental vector control interventions to complement current malaria control activities. As areas are nearing malaria elimination, it is important to re-evaluate environmental risk factors and employ appropriate interventions to effectively address low-level malaria transmission.

Continuous Cultures of Plasmodium Falciparum Established in Tanzania from Patients with Acute Malaria.

BACKGROUND: Malaria morbidity and mortality, almost entirely from Plasmodium falciparum, are still rampant in Africa: therefore, it is important to study the biology of the parasite and the parasite-host cell interactions. In vitro cultivation of Plasmodium falciparum is most useful for this purpose, as well as for investigating drug resistance and possible new therapies. Here we report that the Trager & Jensen continuous culture of P. falciparum can be established in a laboratory in Tanzania with minimal facilities and with modest expenditure. METHODOLOGY: This was an in-vitro set up of continuous culture of Plasmodium falciparum study, carried out in 2016-2020 at Muhimbili university of health and allied sciences, Dar-es salaam. Parasite samples were obtained from patients with acute malaria, frozen parasites, and live cultures. Data was collected and analyzed using GraphPad Prism version 8. RESULTS: We have successfully achieved exponential growth of existing strains that are used worldwide, as well as of parasites in clinical samples from patients with acute malaria. In the aim to optimize growth we have compared human serum and bovine serum albumin as components of the culture media. Additionally, culture synchronization has been achieved using sorbitol. CONCLUSION: This experimental system is now available to our institution and to researchers aiming at investigating drug sensitivity and mechanisms of protection against Plasmodium falciparum that accrue from various genes expressed in red cells.

A systematic review and meta-analysis on the rate of human schistosomiasis reinfection.

While praziquantel mass drug administration is currently the most widely used method in the control of human schistosomiasis, it does not prevent subsequent reinfection hence persistent transmission. Towards schistosomiasis elimination, understanding the reinfection rate is crucial in planning for the future interventions. However, there is scarcity of information on the global reinfection rate of schistosomiasis. This systematic review and meta-analysis aimed at summarizing studies that estimated the reinfection rate of human schistosomiasis. Three data bases (PubMed, Hinari and Google Scholar) were thoroughly searched to retrieve original research articles presenting data on reinfection rate of human schistosomiasis. Study quality and risk of bias was assessed based on Joanna Briggs Institute critical appraisal checklist. Meta-analysis was conducted using statistical R version 3.6.2 and R Studio using "meta" and "metafor" packages. Random effect model was employed to estimate pooled reinfection rates. Heterogeneity was determined using Cochran's Q (chi-square)-test and Higgins I2 statistics. A total of 29 studies met inclusion criteria to be included in this review. All studies had at least satisfactory (5-9 scores) quality. The overal mean and pooled reinfection rates of schistosomiasis were 36.1% (±23.3%) and 33.2% (95% CI, 26.5-40.5%) respectively. For intestinal schistosomiasis, the mean and pooled reinfection rates were 43.9% (±20.6%) and 43.4% (95% CI, 35.8-51.4%), and that for urogenital schistosomiasis were 17.6% (±10.8%) and 19.4% (95% CI, 12.3%- 29.2%) respectively. Cochran's Q (chi-square)-test and Higgins I2 statistic indicated significant heterogeneity across studies (p-values < 0.001, I2 values > 95%). Results of subgroup analysis showed that, the type of Schistosoma species, participants' age group, sample size and geographical area had influence on disparity variation in reinfection rate of schistosomiasis (p < 0.1). Despite the control measures in place, the re-infection rate is still high, specifically on intestinal schistosomiasis as compared to urogenital schistosomiasis. Achieving 2030 sustainable development goal 3 on good health and wellbeing intensive programmatic strategies for schistosomiasis elimination should be implemented. Among such strategies to be used at national level are repeated mass drug administration at least every six months, intensive snails control and health education.