Risk factors for non-participation in ivermectin and dihydroartemisinin-piperaquine mass drug administration for malaria control in the MASSIV trial.

BACKGROUND: Mass Drug Administration (MDA) has become a mainstay for the control of several diseases over the last two decades. Successful implementation of MDA programmes requires community participation and can be threatened by systematic non-participation. Such concerns are particularly pertinent for MDA programmes against malaria, as they require multi-day treatment over several consecutive months. Factors associated with non-participation to the MDA campaign with ivermectin (IVM) and dihydroartemisinin-piperaquine (DHP) implemented within the MASSIV cluster randomized trial were determined. METHODS: Coverage data was extracted from the MASSIV trial study database, with every datapoint being a directly observed therapy (DOT). A complete month of MDA was classified as receiving all three daily doses of treatment. For both ivermectin and DHP, ordinal logistic regression was used to identify individual and household level variables associated with non-participation. RESULTS: For ivermectin, 51.5% of eligible participants received all 3 months of treatment while 30.7% received either one or two complete months. For DHP, 56.7% of eligible participants received all 3 months of treatment and 30.5% received either one or two complete months. Children aged 5-15 years and adults aged more than 50 years were more likely to receive at least one complete month of MDA than working age adults, both for ivermectin (aOR 4.3, 95% CI 3.51-5.28 and aOR of 2.26, 95% CI 1.75-2.95) and DHP (aOR 2.47, 95%CI 2.02-3.02 and aOR 1.33, 95%CI 1.01-1.35), respectively. Members of households where the head received a complete month of MDA were more likely to themselves have received a complete month of MDA, both for ivermectin (aOR 1.71, 95%CI 1.35-2.14) and for DHP (aOR 1.64, 95%CI 1.33-2.04). CONCLUSION: Personal and household-level variables were associated with participation in the MDA programme for malaria control. Specific strategies to (increase participation amongst some groups may be important to ensure maximum impact of MDA strategies in achieving malaria elimination. TRIAL REGISTRATION: The MASSIV trial is registered under NCT03576313.

Effects of ivermectin mass drug administration for malaria vector control on ectoparasites and soil-transmitted helminths: a cluster randomized trial.

OBJECTIVES: Ivermectin, used to control several neglected tropical diseases, may also reduce malaria transmission. Mass drug administration (MDA) for malaria control therefore might have off-target impacts on neglected tropical diseases. METHODS: In The Gambia, nested in a trial of ivermectin MDA, cross-sectional surveys measuring ectoparasites and soil-transmitted helminths in children aged 3 to 14 years took place in June and November 2019 and in November 2021. RESULTS: After MDA, scabies prevalence was 41.2% (237/576) in the control and 38.2% (182/476) in the intervention arm (odds ratio [OR] 0.89 (95% confidence interval [CI] 0 67-1.2), P-value = 0.471) but by 2021, had rebounded to 38.8% (180/464) in the control and 53.2% (245/458) in the intervention arm. After MDA, prevalence of Strongyloides stercoralis was 16.8% (87/518) in the control and 9.1% (40/440) in the intervention arm (OR 0.4 (95% CI 0.16-0.94), P-value = 0.039). In 2021, it was 9.2% (38/413) in the control and 11.3% (45/399) in the intervention arm (OR 1.31 (95% CI 0.74-2.28), P-value = 0.35). CONCLUSION: Scabies prevalence was similar between the two study arms. S. stercoralis prevalence was reduced. However, this effect did not last long: the prevalence 2 years after MDA was similar between study arms.

Broadening the range of use cases for ivermectin - a review of the evidence.

Ivermectin is a broad-spectrum antiparasitic agent that interferes with glutamate-gated chloride channels found in invertebrates but not in vertebrate species. Mass drug administration (MDA) with ivermectin-based regimes has been a mainstay of elimination efforts targeting onchocerciasis and lymphatic filariasis for more than 3 decades. More recently, interest in the use of ivermectin to control other neglected tropical diseases (NTDs) such as soil-transmitted helminths and scabies has grown. Interest has been further stimulated by the fact that ivermectin displays endectocidal efficacy against various Anopheles species capable of transmitting malaria. Therefore there is growing interest in using ivermectin MDA as a tool that might aid in the control of both malaria and several NTDs. In this review we outline the evidence base to date on these emerging indications for ivermectin MDA with reference to clinical and public health data and discuss the rationale for evaluating the range of impacts of a malaria ivermectin MDA on other NTDs.

Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial.

BACKGROUND: With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. OBJECTIVE: The study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. METHODS: The study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. RESULTS: The MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. CONCLUSIONS: This is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/20904.

Impact of Community Treatment With Ivermectin for the Control of Scabies on the Prevalence of Antibodies to Strongyloides stercoralis in Children.

The prevalence of antibodies to Strongyloides stercoralis was measured in 0-12-year-olds using a bead-based immunoassay before and after ivermectin mass drug administration (MDA) for scabies in the Solomon Islands. Seroprevalence was 9.3% before and 5.1% after MDA (P = .019), demonstrating collateral benefits of ivermectin MDA in this setting.

Taenia solium cysticercosis and taeniasis in urban settings: Epidemiological evidence from a health-center based study among people with epilepsy in Dar es Salaam, Tanzania.

In Africa, urbanization is happening faster than ever before which results in new implications for transmission of infectious diseases. For the zoonotic parasite Taenia solium, a major cause of acquired epilepsy in endemic countries, the prevalence in urban settings is unknown. The present study investigated epidemiological, neurological, and radiological characteristics of T. solium cysticercosis and taeniasis (TSCT) in people with epilepsy (PWE) living in Dar es Salaam, Tanzania, one of the fastest growing cities worldwide. A total of 302 PWE were recruited from six health centers in the Kinondoni district of Dar es Salaam. Serological testing for T. solium cysticercosis-antigen (Ag) and -antibodies (Abs) and for T. solium taeniasis-Abs was performed in all PWE. In addition, clinical and radiological examinations that included cranial computed tomography (CT) were performed. With questionnaires, demographic data from study populations were collected, and factors associated with TSCT were assessed. Follow-up examinations were conducted in PWE with TSCT. T. solium cysticercosis-Ag was detected in three (0.99%; 95% CI: 0-2.11%), -Abs in eight (2.65%; 95% CI: 0.84-4.46%), and taeniasis-Abs in five (1.66%; 95% CI: 0.22-3.09%) of 302 PWE. Six PWE (1.99%; 95% CI: 0.41-3.56%) were diagnosed with neurocysticercosis (NCC). This study demonstrates the presence of TSCT in Dar es Salaam, however, NCC was only associated with a few cases of epilepsy. The small fraction of PWE with cysticercosis- and taeniasis-Abs may suggest that active transmission of T. solium plays only a minor role in Dar es Salaam. A sufficiently powered risk analysis was hampered by the small number of PWE with TSCT; therefore, further studies are required to determine the exact routes of infection and risk behavior of affected individuals.

Randomized Trial of Community Treatment With Azithromycin and Ivermectin Mass Drug Administration for Control of Scabies and Impetigo.

BACKGROUND: Scabies is a public health problem in many countries, with impetigo and its complications important consequences. Ivermectin based mass drug administration (MDA) reduces the prevalence of scabies and, to a lesser extent, impetigo. We studied the impact of co-administering azithromycin on the prevalence of impetigo and antimicrobial resistance. METHODS: Six communities were randomized to receive either ivermectin-based MDA or ivermectin-based MDA co-administered with azithromycin. We measured scabies and impetigo prevalence at baseline and 12 months. We collected impetigo lesions swabs at baseline, 3 and 12 months to detect antimicrobial resistance. RESULTS: At baseline, scabies and impetigo prevalences were 11.8% and 10.1% in the ivermectin-only arm and 9.2% and 12.1% in the combined treatment arm. At 12 months, the prevalences had fallen to 1.0% and 2.5% in the ivermectin-only arm and 0.7% and 3.3% in the combined treatment arm. The proportion of impetigo lesions containing Staphylococcus aureus detected did not change (80% at baseline vs 86% at 12 months; no significant difference between arms) but the proportion containing pyogenic streptococci fell significantly (63% vs 23%, P < .01). At 3 months, 53% (8/15) of S. aureus isolates were macrolide-resistant in the combined treatment arm, but no resistant strains (0/13) were detected at 12 months. CONCLUSIONS: Co-administration of azithromycin with ivermectin led to similar decreases in scabies and impetigo prevalence compared to ivermectin alone. The proportion of impetigo lesions containing pyogenic streptococci declined following MDA. There was a transient increase in the proportion of macrolide-resistant S. aureus strains following azithromycin MDA. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT02775617).

Impact of ivermectin administered for scabies treatment on the prevalence of head lice in Atoifi, Solomon Islands.

BACKGROUND: Scabies and head lice are ubiquitous ectoparasitic infestations that are common across the Pacific Islands. Ivermectin is an effective treatment for both conditions, although the doses used vary. At a community level, mass drug administration (MDA) with ivermectin is an effective strategy to decrease prevalence of scabies. To what extent MDA with ivermectin will also reduce prevalence of head lice is unknown. METHODOLOGY: Head lice prevalence was assessed before and after MDA with oral ivermectin (at a dose of 200 micrograms per kilogram of body weight) administered on day 1 and day 8. The primary outcome was the change in prevalence of head louse infestation at two weeks compared to baseline. Longer term efficacy was assessed three months after MDA. RESULTS: 118 participants were enrolled. Baseline prevalence of active head louse infestation was 25.4% (95% CI 18.4-34.0). At two-week follow-up, prevalence was 2.5% (95% CI 0.9-7.2), a relative reduction of 89.1% (95% CI 72.7-91.4%, p<0.001). At three-month follow-up, prevalence was 7.5% (95% CI 2.7-12.3), a relative reduction of 70.6% (95% CI 72.7%-91.4%, p <0.001). Head louse infestation was associated with younger age (age ≤10 years: prevalence 46.7%; adjusted odds ratio compared to adults of 7.2, 95%CI 2.0-25.9) and with having at least one other member of the household with active head louse infestation (adjusted odds ratio 4.3, 95%CI 1.7-11.1). CONCLUSIONS: Head louse infestation is common in the Solomon Islands. This proof of principle study shows that oral ivermectin at a dose of 200 micrograms per kilogram can reduce the burden of active head louse infestation, offering an additional collateral benefit of MDA with ivermectin for scabies control. TRIAL REGISTRATION: ClinicalTrials.gov NCT03236168.

Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review.

INTRODUCTION: Syphilis continues to be a major public health problem and the recent resurgence in syphilis in high-income settings has seen an accompanying increase in cases of neurosyphilis. While the introduction of PCR has had a significant impact on the diagnosis of early syphilis, cerebrospinal fluid (CSF) serological assays remain the most commonly used tests to diagnosis neurosyphilis. We reviewed data on the performance of CSF-PCR for the diagnosis of neurosyphilis. METHODS: We searched Pubmed, Medline, EMBASE and the grey literature for references on PCR in neurosyphilis. We calculated the sensitivity and specificity of PCR compared with reference testing for the diagnosis of neurosyphilis. RESULTS: We identified 66 articles of which seven met the study inclusion criteria. The sensitivity of PCR for definite neurosyphilis varied between 40% and 70% and specificity between 60% and 100% across the studies. The most commonly used PCR assay targeted Tp47 which had an overall sensitivity of 68% and a specificity of 91.9%. DISCUSSION: The sensitivity of PCR was low compared with CSF-serological assays but the challenges of evaluating a diagnostic test in the absence of a clear gold standard make definitive interpretation challenging. Most studies were small and not adequately powered highlighting the need for multicentre, multicountry trials to provide adequate statistical power in evaluations of new tests the diagnosis of neurosyphilis.

Incidental mosquitocidal effect of an ivermectin mass drug administration on Anopheles farauti conducted for scabies control in the Solomon Islands.

Background: The Solomon Islands is targeting elimination of malaria by 2030. The dominant vector is the predominantly exophagic, exophilic Anopheles farauti sensu strictu. This biting behaviour limits the efficacy of conventional vector control tools and highlights the need for new strategies. When administered to humans ivermectin has been shown to have a mosquitocidal effect. Mass drug administration (MDA) with ivermectin is an emerging strategy in the control of scabies. In this study we explored any incidental effect of ivermectin MDA conducted for scabies control on mosquitoes. Methods: MDA for scabies was conducted in three villages. We performed human landing catches and measured 5-day mortality amongst Anopheles mosquitoes caught before and after MDA. Cox regression was used to calculate hazard ratios (HR) for mortality between mosquitoes caught before and after MDA. Results: There was a significant increase in 5-day mortality in anopheline mosquitoes caught post-MDA which was highest on the day of MDA itself (HR 4.2 95% CI 1.8 to 10.1, p=0.001) and the following day (HR 4.4 95% CI 1.8 to 10.8, p=0.002) compared to mosquitoes caught before MDA. Conclusions: This study shows a possible mosquitocidal effect of ivermectin MDA conducted for scabies control. Studies with a larger sample size with clinical as well as entomological outcomes should be conducted in this population.

Association between Taenia solium infection and HIV/AIDS in northern Tanzania: a matched cross sectional-study.

BACKGROUND: The frequency of Taenia solium, a zoonotic helminth, is increasing in many countries of sub-Saharan Africa, where the prevalence of the human immunodeficiency virus (HIV) is also high. However, little is known about how these two infections interact. The aim of this study was to compare the proportion of HIV positive (+) and negative (-) individuals who are infected with Taenia solium (TSOL) and who present with clinical and neurological manifestations of cysticercosis (CC). METHODS: In northern Tanzania, 170 HIV+ individuals and 170 HIV- controls matched for gender, age and village of origin were recruited. HIV staging and serological tests for TSOL antibodies (Ab) and antigen (Ag) were performed. Neurocysticercosis (NCC) was determined by computed tomography (CT) using standard diagnostic criteria. Neurological manifestations were confirmed by a standard neurological examination. In addition, demographic, clinical and neuroimaging data were collected. Further, CD4+ cell counts as well as information on highly active antiretroviral treatment (HAART) were noted. RESULTS: No significant differences between HIV+ and HIV- individuals regarding the sero-prevalence of taeniosis-Ab (0.6% vs 1.2%), CC-Ab (2.4% vs 2.4%) and CC-Ag (0.6% vs 0.0%) were detected. A total of six NCC cases (3 HIV+ and 3 HIV-) were detected in the group of matched participants. Two individuals (1 HIV+ and 1 HIV-) presented with headaches as the main symptom for NCC, and four with asymptomatic NCC. Among the HIV+ group, TSOL was not associated with CD4+ cell counts, HAART duration or HIV stage. CONCLUSIONS: This study found lower prevalence of taeniosis, CC and NCC than had been reported in the region to date. This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC. Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself.

[A fever of finally known origin]. / FUO - alles in Butter?

We present the case of a 77 year old man with fever of unknown origin. Despite a thorough assessment in hospital the diagnosis could only be made after discharge when positive results for C. burnetii serology revealed acute Q-fever. However, retrospectively history and clinical findings matched well with acute Q-fever.

Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria.

BACKGROUND: Experimental murine malaria has been shown to result in significant hearing impairment. Microscopic evaluation of the temporal bones of these animals has revealed regular morphology of the cochlea duct. Furthermore, the known vascular pathologic changes being associated with malaria could not be found. Immunohistochemistry for ICAM1 showed a strong marking in the stria vascularis, indicating a disturbance of the endocochlear potential. The aim of this study was to evaluate the role of apoptosis and the disturbance of the blood labyrinth barrier in the murine malaria associated hearing impairment. METHODS: The temporal bones of seven mice with cerebral malaria-four with hearing impairment, three without hearing impairment-were evaluated with immunohistochemistry for cleaved caspase 3 to detect apoptosis and connexin 26, a gap junction protein being a cornerstone in the endocochlear potassium recirculation. Furthermore five animals with cerebral malaria were treated with Evans blue prior to sacrification to detect disturbances of the blood labyrinth barrier. RESULTS: Cleaved caspase 3 could clearly be detected by immunohistochemistry in the fibrocytes of the spiral ligament, more intensively in animals with hearing impairment, less intensively in those without. Apoptosis signal was equally distributed in the spiral ligament as was the connexin 26 gap junction protein. The Evans blue testing revealed a strong signal in the malaria animals and no signal in the healthy control animals. CONCLUSION: Malfunction of the fibrocytes type 1 in the spiral ligament and disruption of the blood labyrinth barrier, resulting in a breakdown of the endocochlear potential, are major causes for hearing impairment in murine cerebral malaria.

Murine cerebral malaria: histopathology and ICAM 1 immunohistochemistry of the inner ear.

OBJECTIVE: To evaluate the pathophysiologic changes in the inner ear during the course of severe cerebral malaria in an established animal model, C57 BL/6J mice. METHODS: This study aims to examine the hearing threshold, the histological changes and ICAM-1 expression in the murine cochlea. RESULTS: Four of seven mice showed an expected hearing loss of 20 dB or more. The light microscopy of the inner ear did not show any morphologic alterations. The immunohistochemical analysis for ICAM-1 showed intensive staining in the stria vascularis of sick animals and hardly any reaction in healthy controls. CONCLUSION: The up-regulation of ICAM-1 in the stria vascularis - generating the endocochlear potential - suggests its involvement in plasmodial infection.

Murine malaria is associated with significant hearing impairment.

BACKGROUND: Plasmodium falciparum malaria has been suspected to cause hearing loss. Developmental, cognitive and language disorders have been observed in children, surviving cerebral malaria. This prospective study aims to evaluate whether malaria influences hearing in mice. METHODS: Twenty mice were included in a standardized murine cerebral malaria model. Auditory evoked brainstem responses were assessed before infection and at the peak of the illness. RESULTS: A significant hearing impairment could be demonstrated in mice with malaria, especially the cerebral form. The control group did not show any alterations. No therapy was used. CONCLUSION: This suggests that malaria itself leads to a hearing impairment in mice.