Clinton Foundation

Abstract Adverse drug reactions (ADRs) remain a major barrier to successful tuberculosis (TB) treatment. They undermine adherence, prolong morbidity, and increase the risk of treatment failures and mortality. Yet, evidence on their incidence, duration, and management across diverse patient groups remains limited. We conducted a mixed-methods study to address this gap, using a representative sample of patients from six states in India. Specifically, we combined ethnographic observations and interviews with 40 patients and stakeholders across three districts with a quantitative survey of 2,000 randomly selected TB patients across eight districts. The ethnographic analysis revealed a novel taxonomy of ADRs, distinguishing active ADRs (acute, clinically urgent conditions), from passive ADRs (persistent, lower-intensity conditions) that quietly undermine adherence in later treatment phases. Passive ADRs such as skin darkening and fatigue typically warrant little clinical attention, yet their persistence makes them highly relevant for patient management strategies aimed at supporting adherence and achieving TB elimination. This finding was further contextualized and strengthened by quantitative analysis, which provided robust statistical insights into their incidence across diverse patient profiles. The quantitative analyses also reveal a near-universal burden of ADRs, with 86% of patients reporting at least one ADR (Mean = 3.1, SD 2.38). Women reported ADRs more frequently and for longer durations, particularly cutaneous ADRs, while elderly patients were more prone to gastrointestinal and musculoskeletal ADRs. Younger patients and women reported the highest prevalence of vomiting (41%), which emerged as the only independent predictor of unsuccessful treatment completion (OR = 0.39, 95% CI: 0.20–0.76). The overall number of ADRs was also strongly correlated with adverse treatment outcomes (OR = 0.88, 95% CI: 0.78–0.98). The active-passive taxonomy, along with risk-group profiling, offers a roadmap for differentiated counselling and pro-active patient-centric ADR management. We recommend embedding this approach into national TB protocols, with structured risk-based patient counselling at different stages of treatment, supported by adequate training for treatment coordinators and providers. While further research is warranted to assess scalability and cost-effectiveness, our findings demonstrate both the urgency and the feasibility of structured ADR management in high-burden TB settings. Author Summary Adverse drug reactions (ADRs) among drug-sensitive TB patients pose a significant challenge in TB treatment, particularly in resource-constrained settings. Yet, literature on their incidence, duration and resolutions pathways remains scarce - especially studies documenting these across socio-demographic profiles. Our study addresses this gap using a sequential mixed-methods design, combining qualitative and quantitative methodologies. The approach contributes two key advances to the literature. First, it introduces a novel taxonomy of ADRs, grounded in patients’ lived experiences and the support received. This taxonomy segregates ADRs into “active” ADRs, which are more severe and require urgent medical attention, and “passive” ADRs, which are less severe but persist for a longer time, and quietly undermine adherence. Second, it provides statistically validated evidence on the incidence, duration, and resolution of eleven ADRs, disaggregated across socio-demographic profiles. Together, these findings provide a roadmap for developing differentiated, risk-tailored protocols that emphasize gender- and age-responsive counselling. We recommend adapting these insights to inform dedicated ADR guidance within the National TB Elimination Frameworks (NTEP) for India, as well as other high-burden countries, clearly outlining the roles and responsibilities of healthcare providers - particularly treatment coordinators and physicians - and supporting them through targeted training led in collaboration with the NTEP.

BackgroundThe cestode Dipylidium caninum is known to infect dogs via the ingestion of an intermediate flea host, typically Ctenocephalides felis. Simparica Trio® is an oral combination drug product for dogs effective in the treatment and prevention of fleas, including C. felis. Here, we report two laboratory studies evaluating the efficacy of a single administration of Simparica Trio at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin, and 5 mg/kg pyrantel (as pamoate salt) in preventing D. caninum infection in dogs for 1 month through killing of C. felis.MethodsA total of 20 dogs (n = 10 per group) proven to be suitable hosts for C. felis were used in each of the two studies. Treatment occurred on day 0, with each dog given either the placebo or Simparica Trio. On days 0 (after treatment), 7, 14, 21, and 30, dogs were infested using 200 (± 5) unfed D. caninum-infected C. felis. Live flea counts were conducted on day 33 (72 ± 2 h after day 30 infestation). All dogs were euthanized on day 58, and each dog was necropsied for the recovery of D. caninum scolexes from the gastrointestinal tract.ResultsPlacebo-treated dogs had adequate flea infestations and cestode infections in both studies. Simparica-Trio-treated dogs were free of fleas on day 33 (100% efficacy) and had significantly lower mean flea counts compared with placebo-treated dogs (P ≤ 0.0007). Scolex counts in Simparica-Trio-treated dogs were also significantly decreased compared with placebo-treated dogs in both studies. The efficacy of Simparica Trio against D. caninum based on least squares mean scolex counts was 100% (P < 0.0001) in study 1 and 92.1% (P = 0.0033) in study 2.ConclusionsThe efficacy provided by Simparica Trio against C. felis at the minimum dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin, and 5 mg/kg pyrantel (as pamoate salt) prevented D. caninum infection in dogs for 1 month.Graphical

IntroductionImmunisation coverage in low- and middle-income countries continues to face challenges due to persistent gaps in vaccination schedule knowledge among caregivers and health workers. The Routine Immunisation Wheel was developed as a low-cost visual tool to complement existing systems like Mother Child Protection (MCP) cards and community healthcare worker visits in Madhya Pradesh, India. This pilot study evaluates the tool’s effectiveness on improving knowledge and awareness among caregivers and frontline workers (FLWs), as well as its potential for scaling within routine immunisation programs.MethodologyUsing a mixed-methods approach, we conducted a quasi-experimental pilot comparing intervention and control districts with 384 caregivers per arm and more than 60 FLWs (vaccinators/Auxiliary Nurse Midwife (ANMs), mobilizers Accredited Social Health Activists (ASHAs) and Anganwadi Workers (AWWs). Statistical analysis included descriptive statistics for demographics, mean scores with 95% confidence intervals for knowledge domains, independent samples t-tests for group comparisons, chi-square tests for proportions, and thematic analysis of qualitative feedback.ResultsAt endline, caregiver knowledge scores in the intervention district were higher than at baseline for immunisation schedule (mean: 53.7% vs. 35.6%, p < 0.05), immunisation benefits (mean: 87.4% vs. 62.5%, p < 0.05), and session site awareness (95.1% vs. 89.8%, p < 0.05). When compared with the control district at endline, the intervention district had, on average, higher scores for immunisation schedule knowledge, immunisation benefits and session site awareness (all p < 0.05). The tool demonstrated high utility among health workers, with 100% adoption by ANMs for due listing and counselling.ConclusionThe routine immunisation wheel effectively addresses critical knowledge gaps in routine immunisation through its dual functionality as both caregiver reminder and healthcare worker job aid. These results highlight its potential for integration into broader immunisation strategies, especially in low-literacy, resource-limited settings.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-025-25318-z.

Revolution® Plus is a topical combination drug product containing selamectin and sarolaner that has been proven effective against the cat flea Ctenocephalides felis, the intermediate host of the cestode Dipylidium caninum. Here, we report two studies evaluating the efficacy of a single administration of Revolution Plus in preventing D. caninum infection in cats for 1 month through killing of the flea intermediate host. Two studies (study 1 and 2) with the same design were conducted. In both studies, 2 treatment groups of ten cats each were enrolled. On Day 0, the cats in group 1 were treated with a placebo, and the cats in group 2 were treated with Revolution Plus at the minimum recommended dose of 6.0mg/kg selamectin and 1.0mg/kg sarolaner. After treatment on Day 0, as well as on Days 7, 14, 21, and 30, the cats in both treatment groups were infested with 100 (± 5) unfed, D. caninum-infected fleas. Live flea counts were conducted on Day 33 (72 ± 2h after Day 30 infestation). All cats were euthanized on Day 58, and necropsies were performed to enumerate D. caninum scolices in the gastrointestinal tract. In both study 1 and 2, all placebo-treated cats were infested with two or more D. caninum scolices at necropsy. Significantly lower mean flea counts were recorded for the Revolution Plus-treated cats compared with placebo-treated cats (P ≤ 0.0001), and efficacy based on least squares mean flea counts on Day 33 was 100% (in study 1) and 94.3% (in study 2). Scolex counts were also significantly decreased in Revolution Plus-treated cats compared with placebo-treated cats, with a 97.1% efficacy in study 1 and a 99.3% efficacy in study 2. One topical administration of Revolution Plus at the minimum dosage of 6.0mg/kg selamectin and 1.0mg/kg sarolaner provided high efficacy in the prevention of D. caninum infection through the killing of its vector, C. felis, for an entire month.

Epilepsy is the most widespread neurological disorder in Africa, affecting an estimated 25 million people. The disorder is characterized by recurrent seizures, which can be caused by a variety of factors, including past trauma, central nervous system infections, and genetic disorders. Diagnosis and treatment of epilepsy are challenging in African patients due to several factors, including the low socioeconomic status of the residents and limited access to appropriate medication. Phenobarbital remains the only drug widely available to patients, but it is not always effective and can have significant side effects. In addition to the medical challenges, individuals with epilepsy also face a lot of social stigmas in Africa. Widespread superstitions and false beliefs lead to prejudices against these people, making it difficult for them to live fulfilling social lives. With the development of new treatment modalities, such as gene therapy, stem cell therapy, and P-glycoprotein inhibitors, it is more important now than ever to increase the research output for the African region to create the best possible treatment and maximize patient outcomes.

Abstract Mobile health applications called Digital Adherence Technologies (DATs) are increasingly used for improving treatment adherence among Tuberculosis patients to attain cure, and/or other chronic diseases requiring long term and complex medication regimens. These DATs are found to be useful in resource limited settings because of their cost efficiency in reaching out to vulnerable groups (providing pill &amp; clinic visit reminders, health information and awareness on the disease along with motivational messages and support to be retained in care) or those staying in remote or rural areas. Despite their growing ubiquity, there is very limited evidence on how they improve healthcare outcomes. We analyze the uptake of such an intervention in an urban setting (DS-DOST, powered by Connect for LifeTM, Johnson &amp; Johnson) among different patient groups accessing TB services in New Delhi, India, and subsequently assess its impact in improving patient engagement and treatment outcomes. This study aims to understand the uptake patterns of a digital adherence technology and its impact in improving follow ups and treatment outcomes among TB patients. Propensity choice modelling was used to create balanced treated and untreated patient datasets, before applying simple ordinary least square and logistic regression methods to estimate the causal impact of the intervention on the number of follow ups made with the patient and treatment outcomes.After controlling for potential confounders, it is found that patients who installed and utilized DS-DOST application received an average of 6.4 (95% C.I. [5.32 to 7.557]) additional follow-ups, relative to those who did not utilize the application. This translates to a 58% increase. They also had 245% higher likelihood of a treatment success (Odds ratio: 3.458; 95% C.I. [1.709 to 6.996]). Descriptive results indicate that young females, and those suffering from pulmonary tuberculosis have a slightly higher propensity to use the CfL™ app, and benefit through their treatment duration.Author SummaryThe research tries to understand the impact of using cost-effective digital adherence tools, in improving treatment outcomes among patients diagnosed with drug-sensitive Tuberculosis (TB). As the treatment duration for TB is fairly long (at least 6 months) and complicated (multiple drugs, typically given in two distinct phases), there are challenges associated with ensuring treatment adherence. The research finds that digital tools such as a mobile application – can be a useful aid, albeit only when they are used in conjunction with the support of a healthcare worker. The digital tool analyzed, while sending medication reminders to patients, also enabled healthcare workers in tracking adherence for their assigned patients. The latter, as the research finds, ensured that they follow up with their patients to ensure adherence, resulting in increased odds of their getting a favourable treatment outcome. Further, the study underscores that a digital intervention used in isolation might not draw a favourable impact among patients – highlighting the role of healthcare workers and tailored interventions. In conclusion, digital adherence technologies can act as cost-effective measures in empowering healthcare workers to support their patients, and subsequently improve treatment outcomes.

Highlights The presence of lymphadenopathy distinguishes monkeypox from smallpox, and the subsequent complications include encephalitis, bronchopneumonia, secondary infections, sepsis, corneal infections, and vision loss. Viral encephalitis, seen in various countries in association with monkeypox, can cause various neurologic complications ranging from altered mental status to seizures and focal neurologic deficits. There should be campaigns to raise knowledge of the clinical symptoms, transmission pathways, diagnosis, consequences, and prevention of this virus. Further prevention efforts should be made by the ministry of health, especially in endemic regions. Monkeypox virus (MPX), which is one of the four pathogenic species affecting humans along with cowpox, vaccinia, and variola viruses, belonging to the Orthopoxvirus genus in the family Poxviridae, is considered to be the causative agent of the advancing zoonotic disease MPX1. Once the virus enters the body from any route, oropharynx, nasopharynx, or intradermal, it will replicate at that respective site and then spread to local lymph nodes. Clinically, MPX has an incubation period of 1–2 weeks2. The prodrome illness then begins with a fever of no more than 40.5°C. Patients usually complain of headache, malaise, and typical lymph node enlargement, particularly, the mandibular, cervical, or inguinal nodes1,3. The lesions persist between 2 and 4 weeks and develop at the same stage. They are centrifugal, umbilicated, and hard2,3. Despite the fact that the detailed dermatological manifestations are abundantly found in the literature, the neurological complications of this viral infection have yet to be properly documented and characterized. However, MPX has been reported to affect the central nervous system (CNS) with encephalitis being the most common neurological complication3,4. Furthermore, due to overlapping similarities between MPX and smallpox viruses, we can propose that the neurological complications of this viral infection can be significant. For instance, encephalopathy is the most common complication of smallpox infection, and while encephalitis, seizures, and strokes are less commonly seen, they are still documented following both viral smallpox-related infections as well as vaccinations with Vaccinia5. Although rarely stated in the literature, encephalitis associated with MPX infection seems to behave similarly to viral encephalitis. Thus, MPX-associated encephalitis can infect the CNS retrogradely via nerve terminals or haematogenous dissemination. Once the virus enters the CNS, it replicates and disrupts neuron cell function, leading to cerebral edema, vascular congestion, and intracranial hemorrhage6. Clinically patients with encephalitis usually present with altered mental status, changes in the level of consciousness, personality changes, generalized or partial seizures, or focal neurological findings. Electroencephalographymight also show epileptiform changes7. Also, cerebrospinal fluid analysis of a patient with MPX-associated encephalitis may show MPX-specific immunoglobulin M antibodies8. It should be noted that patients with encephalitis might die or require admission to the ICU and even mechanical ventilation4. The best way to prevent viral encephalitis is to prevent viral infection. For instance, prevention from direct contact with primates and rodents, prevention from blood exposure and avoiding undercooked meat are ways to prevent transmission of the virus from its animal reservoir to humans6. In healthcare settings, infection-control measures should be implemented to prevent human-to-human transmission, such as proper sanitation and isolation of infected patients (Fig. 1). Vaccines against the smallpox virus, ACAM2000, have shown crossed immunity against the MPX virus8. Furthermore, the United States of America Food and Drug Administration has approved JYNNEOS, a vaccine against both smallpox and MPX viruses, for adults that are at high risk of infection. The Centers for Disease Control and Prevention recommends prophylaxis for those with a higher risk of exposure to the virus, however widespread vaccination during the 2022 outbreak is not recommended9. Lastly, the management of MPX depends on the severity. The majority of patients have mild disease. Mild cases require conservative management comprising fluid replenishment, antipyretics, and oxygenation10. However, patients who have or are at risk of dehydration, those who necessitate pain management, and those experiencing severe disease or complications, require hospitalization, and supportive care. For more severe complications, antiviral therapy may be indicated for patients with or at risk of severe disease (i.e. <8 years of age, breastfeeding and pregnant women, patients suffering from complicated infections, as well as immunocompromised patients), as well as patients with the infection affecting atypical sites (i.e. mouth, eyes, and genital area) 11.Figure 1: Summary – neurological complications of monkeypox viral infection, presentation, diagnosis, and management. CSF indicates cerebrospinal fluid; DRC, democratic republic of congo; IgM, immunoglobulin.Ethical approval Not applicable. Sources of funding None. Author contribution O.U.: conceptualization, project administration, and writing – review and designing. Figure 1 was drawn and analyzed by author K.A.D. Manuscript writing, data collection and assembly, and final approval of manuscript by all authors Conflicts of interest disclosure Not applicable. Guarantor Abubakar Nazir, Oli Health Magazine Organization, Kigali, Rwanda. E-mail: [email protected]. ORCID ID: 0000-0002-6650-6982