Therapeutic efficacy of pyronaridine-artesunate (Pyramax®) against uncomplicated Plasmodium falciparum infection at Hamusit Health Centre, Northwest Ethiopia.

BACKGROUND: Early case detection and prompt treatment are important malaria control and elimination strategies. However, the emergence and rapid spread of drug-resistant strains present a major challenge. This study reports the first therapeutic efficacy profile of pyronaridine-artesunate against uncomplicated Plasmodium falciparum in Northwest Ethiopia. METHODS: This single-arm prospective study with 42-day follow-up period was conducted from March to May 2021 at Hamusit Health Centre using the World Health Organization (WHO) therapeutic efficacy study protocol. A total of 90 adults ages 18 and older with uncomplicated falciparum malaria consented and were enrolled in the study. A standard single-dose regimen of pyronaridine-artesunate was administered daily for 3 days, and clinical and parasitological outcomes were assessed over 42 days of follow-up. Thick and thin blood films were prepared from capillary blood and examined using light microscopy. Haemoglobin was measured and dried blood spots were collected on day 0 and on the day of failure. RESULTS: Out of 90 patients, 86/90 (95.6%) completed the 42-day follow-up study period. The overall PCR-corrected cure rate (adequate clinical and parasitological response) was very high at 86/87 (98.9%) (95% CI: 92.2-99.8%) with no serious adverse events. The parasite clearance rate was high with fast resolution of clinical symptoms; 86/90 (95.6%) and 100% of the study participants cleared parasitaemia and fever on day 3, respectively. CONCLUSION: Pyronaridine-artesunate was highly efficacious and safe against uncomplicated P. falciparum in this study population.

An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol.

Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH . Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021).

Comparison of capillary, venous and buffy coat blood samples in detecting Plasmodium species among malaria suspected patients attending at Hamusite health center. A cross-sectional study.

BACKGROUND: Both capillary and venous blood samples have been interchangeably used for the diagnosis of malaria in Ethiopia. However, Plasmodium parasites are thought to be more concentrated in capillary than in venous blood. Hence, selecting a sample source where parasites are more concentrated is indispensable approach in order to maximize the accuracy of blood film microscopy. Therefore, the present study aimed to compare the detection rate and the parasitemia level of Plasmodium species from conventional capillary and venous blood films, and buffy coat preparations. METHODS: A facility based cross-sectional study was conducted from Feburary to March 2020 among 210 febrile patients attending Hamusite health center, northwest Ethiopia. Capillary and venous blood samples were collected and buffy coat was prepared from each sample. Thin and thick blood films were prepared, stained, and examined microscopically following standard protocol. Data were analysed using Statistical Package for Social Sciences Software version 20 and Med-Calc software version 19.3. RESULTS: Capillary blood buffy coat (61/210, 29.0%) had significantly higher detection rate as compared to capillary (48/210, 22.9%) and venous (42/210, 20.0%) blood films (p < 0.001). However, no significant difference was observed between capillary and venous blood films (p = 0.070) in detecting Plasmodium species. The highest and the lowest mean asexual stage parasite counts were found in capillary blood buffy coat (4692.88) and venous blood (631.43) films, respectively showing significant variations (p < 0.001). Mean gametocyte count was also highest in capillary blood buffy coat (3958.44). As compared to capillary blood buffy coat, the sensitivity of venous blood buffy coat, capillary blood film and venous blood film were 73.8, 78.7, 68.9%, respectively. CONCLUSION: Capillary blood buffy coat samples showed the highest sensitivity in detecting and quantitating malaria parasites that its use should be promoted in clinical settings. However, conventional capillary and venous blood films could be used interchangeably.

Performance evaluation of Baermann techniques: The quest for developing a microscopy reference standard for the diagnosis of Strongyloides stercoralis.

BACKGROUND: Soil-transmitted helminths (STH) are common in low and middle income countries where there is lack of access to clean water and sanitation. Effective diagnosis and treatment are essential for the control of STH infections. However, among STH parasites, Strongyloides stercoralis is the most neglected species, both in diagnostics and control strategies. Diagnostic methods cover different approaches, each with different sensitivities and specificities, such as serology, molecular techniques and microscopy based techniques. Of the later, the Baermann technique is the most commonly used procedure. In the literature, several ways have been described to perform the Baermann method, which illustrates the overall lack of a '(gold) reference standard' method for the diagnosis of S. stercoralis infection. In this study we have evaluated the performance of three Baermann techniques in order to improve the reference standard for the microscopic diagnosis of S. stercoralis infection thereby facilitating individual case detection, mapping of the disease and proper evaluation of treatment responses. METHODS/PRINCIPAL FINDINGS: A community based cross sectional study was conducted at Zenzelima, Bahir Dar Zuria Ethiopia. A total of 437 stool samples were collected and analyzed by the following procedures: conventional Baermann (CB), modified Baermann (MB), and modified Baermann with charcoal pre-incubation (MBCI). The diagnostic sensitivity and Negative Predictive Value (NPV) of each technique was calculated using the combination of all the three techniques as a composite reference standard. Our result indicated that larvae of S. stercoralis were detected in 151 (34.6%) stool samples. The prevalence of S. stercoralis infection based on the three diagnostic methods was 9.6%, 8.0%, and 31.3% by CB, MB, and MBCI respectively. The sensitivity and NPV for CB, MB, and MBCI were 26.7% and 70.8%, 22.1% and 69.6%, and 87.0% and 93.2%, respectively. The MBCI showed significant difference (P- value = <0.001) in the sensitivity and NPV values when compared with CB and MB values. The agreement between CB, MB, and MBCI with the composite reference standard was 31.8%, 26.7%, 89.6%, respectively. CONCLUSION/SIGNIFICANCE: Our results suggest the superior performance of MBCI. It is relatively easy to implement, simple to perform and comparatively cheaper. The CB is by far the commonly used method in routine diagnostic although this technique significantly underestimates the true burden of the disease and thereby contributing to the exclusion of S. stercoralis from the control strategies. Therefore, MBCI is recommended as a routine microscopy-based diagnostic test for S. stercoralis infection, particularly in settings where molecular procedures are not available.

The magnitude of Schistosoma mansoni and its associated risk factors among Sebatamit primary school children, rural Bahir Dar, Northwest Ethiopia: a cross-sectional study.

OBJECTIVE: The aim of this study was to determine the magnitude of Schistosoma mansoni and its associated risk factors in the study area. RESULTS: Of 422 school children, 223 (52.8%) and 199 (47.2%) were males and females, respectively. The Overall prevalence of Schistosoma mansoni infection was 24.9% (105/422). Seventy-five out of 422 (71.4%) of the infected individuals showed light infections. The overall mean intensity of Schistosoma mansoni in the study was 106.16 eggs per gram of stool. Age (p = 0.013), swimming habit (p = 0.001), participating in irrigational activities (p = 0.03) and washing clothes in the river (p = 0.039) were factors associated with Schistosoma mansoni infection.

Serological signatures of clinical cure following successful treatment with sodium stibogluconate in Ethiopian visceral leishmaniasis.

BACKGROUND: In Ethiopia, visceral leishmaniasis (VL) is a growing public health threat. Among the key challenges in VL control in Ethiopia is lack of an effective test of cure. The recommended test of cure is parasite detection. As sterile cure is not expected with the current widely used drugs, the value of parasite detection as test of cure is questionable. Moreover, the sampling is invasive, requires a well-equipped facility and highly skilled personnel, which are all hardly found in endemic set-ups. OBJECTIVE: Our aim was to assess the value of sCD40L, MMP9 and IL-10 serum levels as signature biomarkers of clinical cure in VL cases from Ethiopia. METHODS: A total of 45 VL cases before and after treatment and 30 endemic healthy controls were included in the study. Sandwich ELISA was used to measure serum levels of sCD40L, MMP9 and IL-10. RESULT: The mean sCD40L, MMP9 and IL-10 serum levels changed significantly at clinical cure. At individual case level sCD40L and MMP9 showed an increasing trend. Yet, the degree of increase in serum level of MMP9 seems to be affected by nutritional status of the individual VL case. The mean IL-10 serum level was significantly reduced at clinical cure. As seen on case by case basis, all demonstrated a declining trend except that two VL cases had a high IL10 level at clinical cure. CONCLUSION: Our result is suggestive of the possibility of developing a signature biomarker to monitor VL treatment in Ethiopia using one or a combination of parameters.

A Venue-Based Survey of Malaria, Anemia and Mobility Patterns among Migrant Farm Workers in Amhara Region, Ethiopia.

BACKGROUND: Mobile populations present unique challenges to malaria control and elimination efforts. Each year, a large number of individuals travel to northwest Amhara Region, Ethiopia to seek seasonal employment on large-scale farms. Agricultural areas typically report the heaviest malaria burden within Amhara thereby placing migrants at high risk of infection. Yet little is known about these seasonal migrants and their malaria-related risk factors. METHODS AND FINDINGS: In July 2013, a venue-based survey of 605 migrant laborers 18 years or older was conducted in two districts of North Gondar zone, Amhara. The study population was predominantly male (97.7%) and young (mean age 22.8 years). Plasmodium prevalence by rapid diagnostic test (RDT) was 12.0%; One quarter (28.3%) of individuals were anemic (hemoglobin <13 g/dl). Nearly all participants (95.6%) originated from within Amhara Region, with half (51.6%) coming from within North Gondar zone. Around half (51.2%) slept in temporary shelters, while 20.5% regularly slept outside. Only 11.9% of participants had access to a long lasting insecticidal net (LLIN). Reported net use the previous night was 8.8% overall but 74.6% among those with LLIN access. Nearly one-third (30.1%) reported having fever within the past two weeks, of whom 31.3% sought care. Cost and distance were the main reported barriers to seeking care. LLIN access (odds ratio [OR] = 0.30, P = 0.04) and malaria knowledge (OR = 0.50, P = 0.02) were significantly associated with reduced Plasmodium infection among migrants, with a similar but non-significant trend observed for reported net use the previous night (OR = 0.16, P = 0.14). CONCLUSIONS: High prevalence of malaria and anemia were observed among a young population that originated from relatively proximate areas. Low access to care and low IRS and LLIN coverage likely place migrant workers at significant risk of malaria in this area and their return home may facilitate parasite transport to other areas. Strategies specifically tailored to migrant farm workers are needed to support malaria control and elimination activities in Ethiopia.

High prevalence of anti-toxoplasma antibodies and absence of Toxoplasma gondii infection risk factors among pregnant women attending routine antenatal care in two Hospitals of Addis Ababa, Ethiopia.

OBJECTIVE: Toxoplasmosis is an infection caused by the protozoan parasite Toxoplasma gondii. It is acquired mainly by eating raw or undercooked meat containing Toxoplasma gondii tissue cyst, eating food or water contaminated with oocyst, and acquiring congenital infection through the placenta. This study was conducted to determine the prevalence of toxoplasmosis and assess possible risk factors associated with the infection among pregnant women in Addis Ababa, Ethiopia. METHOD: Cross sectional study was designed, and 288 serum samples were collected from November 1(st) 2010 to January 2011. The serum samples were tested for anti- Toxoplasma gondii antibodies using latex agglutination test. The risk factors were tested for significance using Bivariate and multivariate analysis. P-value <0.05 was considered statistically significant. RESULT: 85.4% were positive for anti Toxoplasma gondii antibody. No significant association was observed between seroprevalence and age, gestational age, socio demographic characters, history of abortion, consumption of raw or undercooked meat, consumption of raw vegetable, owning of cat, and blood transfusion. CONCLUSION: Prevalence of toxoplasmosis among pregnant women in Addis Ababa, Ethiopia is higher than that reported from other countries. Efforts to describe risk factors for toxoplasma infection among Ethiopians should focus in children.

Intestinal parasite prevalence in an area of ethiopia after implementing the SAFE strategy, enhanced outreach services, and health extension program.

BACKGROUND: The SAFE strategy aims to reduce transmission of Chlamydia trachomatis through antibiotics, improved hygiene, and sanitation. We integrated assessment of intestinal parasites into large-scale trachoma impact surveys to determine whether documented environmental improvements promoted by a trachoma program had collateral impact on intestinal parasites. METHODOLOGY: We surveyed 99 communities for both trachoma and intestinal parasites (soil-transmitted helminths, Schistosoma mansoni, and intestinal protozoa) in South Gondar, Ethiopia. One child aged 2-15 years per household was randomly selected to provide a stool sample of which about 1 g was fixed in sodium acetate-acetic acid-formalin, concentrated with ether, and examined under a microscope by experienced laboratory technicians. PRINCIPAL FINDINGS: A total of 2,338 stool specimens were provided, processed, and linked to survey data from 2,657 randomly selected children (88% response). The zonal-level prevalence of Ascaris lumbricoides, hookworm, and Trichuris trichiura was 9.9% (95% confidence interval (CI) 7.2-12.7%), 9.7% (5.9-13.4%), and 2.6% (1.6-3.7%), respectively. The prevalence of S. mansoni was 2.9% (95% CI 0.2-5.5%) but infection was highly focal (range by community from 0-52.4%). The prevalence of any of these helminth infections was 24.2% (95% CI 17.6-30.9%) compared to 48.5% as found in a previous study in 1995 using the Kato-Katz technique. The pathogenic intestinal protozoa Giardia intestinalis and Entamoeba histolytica/E. dispar were found in 23.0% (95% CI 20.3-25.6%) and 11.1% (95% CI 8.9-13.2%) of the surveyed children, respectively. We found statistically significant increases in household latrine ownership, use of an improved water source, access to water, and face washing behavior over the past 7 years. CONCLUSIONS: Improvements in hygiene and sanitation promoted both by the SAFE strategy for trachoma and health extension program combined with preventive chemotherapy during enhanced outreach services are plausible explanations for the changing patterns of intestinal parasite prevalence. The extent of intestinal protozoa infections suggests poor water quality or unsanitary water collection and storage practices and warrants targeted intervention.