RESUMO
BACKGROUND: Assessing how interventions are implemented is essential to understanding why interventions may or may not achieve their intended outcomes. There is little evidence about how interventions against Neglected Tropical Diseases (NTDs) are being implemented. Guided by the Context and Implementation of Complex Intervention (CICI) framework, we evaluated an ongoing intervention against the NTD podoconiosis to examine the implementation process and its effectiveness in terms of improving shoe wearing practices, increasing knowledge and reducing stigmatizing attitudes towards podoconiosis in rural Ethiopia. METHODS: We employed an exploratory mixed methods approach, qualitative followed by quantitative, between April and July 2022 to assess implementation agents, theory, strategy, process and outcomes of the intervention. We conducted document analysis, observations, focus group discussions, in-depth interviews and key informant interviews for the qualitative phase. We administered a survey to 369 rural residents, of whom 42 were affected by podoconiosis. RESULTS: The implementers utilized government healthcare centers in a bid to mainstream podoconiosis services within local healthcare structures. The implementers provided training for health professionals and the public and distributed supplies to patients over a three-month period. The intervention reached 62% of patients, but female patients were less likely to participate than male patients. Only 18% of community members had participated in health education campaigns linked to the intervention. Involvement in the intervention resulted in improved shoe wearing practice and holding fewer stigmatizing attitudes. However, internalized stigma among patients was still rife; and the plan to utilize community assets to extend the intervention activities was not effective. CONCLUSIONS: Implementers must monitor the fidelity and progression of programs on a constant basis to make corrections. They also need to expand health education, provide psychosocial support and design economic empowerment programs for patients to reduce stigma. They must also collaborate with policy makers and international partners to sustain program activities at intervention delivery points.
Assuntos
Elefantíase , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Etiópia , Elefantíase/psicologia , Elefantíase/prevenção & controle , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , População Rural , Comportamentos Relacionados com a Saúde , Adulto Jovem , Adolescente , Doenças Negligenciadas/prevenção & controle , IdosoRESUMO
Podoconiosis is a non-infectious, neglected tropical disease caused by chronic barefoot contact with irritant volcanic soils. It typically presents with lower limb swelling, disfigurement, and chronic disability. Patients and their families experience stigma from their communities. Depression, anxiety, and emotional distress contribute to the total illness burden of podoconiosis. This study used a survey-based comparative cross-sectional quantitative study design involving podoconiosis patients, their family members, and unaffected neighbors. The Depression, Anxiety, and Stress Scale (DASS 21), the WHO Quality of Life Scale (WHO-QOL Brief), and the Tekola clinical staging system were used to collect data. We surveyed 741 participants (33.1% patients, 33.3% family, 33.5% neighbors). Podoconiosis patients exhibited significantly elevated odds of severe depression (19.8x), anxiety (10.7x), and stress symptoms (13.5x) in comparison to unaffected neighbors. Family members of podoconiosis patients displayed 1.5x higher odds of experiencing severe anxiety symptoms compared to unaffected neighbors. Higher clinical stages of podoconiosis were associated with increased severity of depressive symptoms. Podoconiosis patients demonstrated lower median scores across all domains of the WHO QoL Brief in contrast to family members and unaffected neighbors. The burden of depression, anxiety, and stress on podoconiosis patients and their family members is high. Podoconiosis morbidity management programs need to encompass families of patients and integrate continuous mental health support within the broader framework of podoconiosis management.
Assuntos
Ansiedade , Depressão , Elefantíase , Saúde Mental , Qualidade de Vida , Humanos , Estudos Transversais , Masculino , Elefantíase/epidemiologia , Elefantíase/psicologia , Feminino , Adulto , Pessoa de Meia-Idade , Depressão/epidemiologia , Ansiedade/epidemiologia , Ruanda/epidemiologia , Adulto Jovem , Idoso , Adolescente , Inquéritos e Questionários , Efeitos Psicossociais da DoençaRESUMO
OBJECTIVE: Given the neglected nature of filariasis, especially in Uganda where data are scarce, this cross-sectional study aimed to determine the sero-antigen prevalence of lymphatic filariasis and risk factors associated with non-lymphatic filariasis (podoconiosis) in Busiriba Sub-county, Kamwenge District, Uganda, during August-September 2018, to inform targeted elimination efforts. RESULTS: We enrolled 101 participants, among whom 35 (34.7%) had podoconiosis. The sero-antigen prevalence of lymphatic filariasis was 1.0%. Older age and walking barefoot were associated with increased podoconiosis risk. Specifically, individuals aged 25-49 years with had 7.38 times higher odds of podoconiosis (adjusted odds ratio [aOR] = 7.38, 95% CI: 1.36-40.13) compared to those under 25 years, while those aged ≥ 50 years had even higher odds (aOR = 8.49, 95%CI: 1.44-50.15). Additionally, individuals who reported walking barefoot had 14 times higher odds of podoconiosis (aOR = 14.08; 95% CI: 2.49-79.50).
Assuntos
Filariose Linfática , Humanos , Uganda/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Fatores de Risco , Estudos Transversais , Filariose Linfática/epidemiologia , Prevalência , Elefantíase/epidemiologia , Adulto Jovem , Idoso , Adolescente , Estudos SoroepidemiológicosRESUMO
OBJECTIVE: This study aimed to assess the impairment of health-related quality of life (HRQoL) and its determinants among patients diagnosed with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia. METHODS: An institutional-based cross-sectional study design was used in the setting of primary healthcare facilities to assess impaired HRQoL among patients with podoconiosis in the East Wollega Zone from 1 March 2023 to 30 April 2023, using the Dermatologic Life Quality Index (DLQI). Data was collected from 494 patients with podoconiosis, and a multistage sampling technique was employed. The data was entered into EpiData V.4.6 and exported to SPSS V.27 for analysis. A linear regression model with a 95% cofidence interval (CI) was used to estimate level of HRQoL and to identify its determinants estimating beta (ß) coefficient declaring the significance level at p<0.05. RESULTS: The quality of life among patients was impaired on average by 9.6±6.1 with the lowest DLQI Score in the domain of treatment (0.8±0.97) and the highest in the domain of daily activity (2.3±1.72). The identified significant determinants of impairment of HRQoL associated with DLQI scores were duration of disease (95% CI, ß=0.11 (0.08 to 0.15)), acute dermato-lymphangio-adenitis (ADLA) (95% CI, ß=0.08 (0.01 to 0.16)), comorbidity (95% CI, ß=1.26 (0.37 to 2.16)), consistently wearing shoes (95% CI, ß=-0.06 (-0.09 to -0.03)), feeling of stigmatised (95% CI, ß=0.21 (0.16 to 0.25)) and psychological distress (95% CI, ß=0.17 (0.14 to 0.21)) and being female (95% CI, ß=1.16 (0.19 to 2.12)). CONCLUSION: Overall, HRQoL among patients with podoconiosis was moderately impaired. The duration of disease, ADLA, comorbidity, stigma, psychological distress and being female in sex significantly impaired HRQoL, whereas consistently wearing shoes significantly improved HRQoL among the patients with podoconiosis. Therefore, healthcare providers and public health experts should work on educating communities and counselling patients to avoid stigma and psychological distress, wearing shoes consistently and treating podoconiosis and other comorbidities among these patients.
Assuntos
Elefantíase , Humanos , Feminino , Masculino , Elefantíase/epidemiologia , Qualidade de Vida , Estudos Transversais , Etiópia/epidemiologia , Estigma SocialRESUMO
BACKGROUND: Podoconiosis is a non-infectious neglected tropical disease caused by long-term exposure to irritant volcanic soils. It results in severe physical, psychological and financial consequences. Heart and Sole Africa (HASA) is a non-governmental, community-based organization providing management to podoconiosis patients in Rwanda. We sought to analyze the impact of their program on the lives of patients. METHODS: Quantitative surveys recorded the participants' demographics, adherence to HASA's management recommendations and changes in quality of life (QOL). Qualitative questions were used to gather respondent perspectives on HASA programming. RESULTS: We interviewed 127 patients from HASA's Musanze (n=47) and Burera (n=80) clinics. Almost all participants (98.4%) reported statistically significant (p<0.01) improvements in their QOL, and more than one-half (51.2%) had a favorable adherence score of >80%. Qualitative feedback identified specific challenges to adherence and recognition of program success in symptom management. CONCLUSIONS: Our study demonstrated the value of community-based podoconiosis programming in improving the lives of patients. Practices such as regular feet washing, emollient application, shoe wearing and limb raising can result in a marked reduction of morbidity. Our findings support the argument for scaling up these management practices across Rwanda.
Assuntos
Elefantíase , Qualidade de Vida , Humanos , Masculino , Feminino , Estudos Transversais , Elefantíase/prevenção & controle , Elefantíase/epidemiologia , Ruanda/epidemiologia , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Educação de Pacientes como AssuntoRESUMO
BACKGROUND: Podoconiosis is a progressive and debilitating form of tropical lymphoedema endemic to Rwanda. Although the physical and psychological consequences are well known, few studies have evaluated the financial burden of podoconiosis. METHODS: This cross-sectional, quantitative study aimed to characterize direct treatment costs and impacts on annual earnings among individuals living with podoconiosis. Participants from two highly endemic districts were invited to complete a survey focused on health-seeking history, insurance status, out-of-pocket costs and income changes. Direct treatment costs included medical expenditures (consultation, diagnostics, medication) and non-medical expenditures (food, transportation, accommodation). RESULTS: Overall, 226 adults (≥18 y of age) diagnosed with podoconiosis participated. Most had access to community-based health insurance (91.6%) but were unable to work (71.7%). Respondents sought care from health centres/posts (61.9%), hospitals (25.1%), traditional healers (5.8%) and/or community health workers (4.0%). On average, study participants paid US$32.50 (range US$0-779.23) annually, or 11.7% of their household salary, on podoconiosis treatments. CONCLUSIONS: This study demonstrates the significant financial burden of podoconiosis on individuals and their communities. Increased attention on integrating podoconiosis management into primary care systems and testing cost-effective solutions is needed to protect those who are most vulnerable.
Assuntos
Efeitos Psicossociais da Doença , Elefantíase , Gastos em Saúde , Renda , Humanos , Masculino , Feminino , Gastos em Saúde/estatística & dados numéricos , Estudos Transversais , Elefantíase/economia , Elefantíase/terapia , Ruanda , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Adolescente , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Available evidences suggest that podoconiosis is triggered by long term exposure of bare feet to volcanic red clay soil particles. Previous genome-wide studies in Ethiopia showed association between the HLA class II region and disease susceptibility. However, functional relationships between the soil trigger, immunogenetic risk factors and the immunological basis of the disease are uncharted. Therefore, we aimed to characterise the immune profile and gene expression of podoconiosis patients relative to endemic healthy controls. Peripheral blood immunophenotyping of T cells indicated podoconiosis patients had significantly higher CD4 and CD8 T cell surface HLA-DR expression compared to healthy controls while CD62L expression was significantly lower. The levels of the activation markers CD40 and CD86 were significantly higher on monocytes and dendritic cell subsets in patients compared to the controls. RNA sequencing gene expression data indicated higher transcript levels for activation, scavenger receptors, and apoptosis markers while levels were lower for histones, T cell receptors, variable, and constant immunoglobulin chain in podoconiosis patients compared to healthy controls. Our finding provides evidence that podoconiosis is associated with high levels of immune activation and inflammation with over-expression of genes within the pro-inflammatory axis. This offers further support to a working hypothesis of podoconiosis as soil particle-driven, HLA-associated disease of immunopathogenic aetiology.
Assuntos
Elefantíase , Humanos , Elefantíase/genética , Histonas , Antígenos CD40 , Linfócitos T CD8-Positivos , ArgilaRESUMO
BACKGROUND: Genetic and genomic research is revolutionizing precision medicine; however, addressing ethical and cultural aspects is crucial to ensure ethical conduct and respect for community values and beliefs. This study explored the beliefs, perceptions and concerns of the Aari community in South Ethiopia regarding genetic concepts, hereditary diseases and ethical research practices related to sample collection, storage and sharing. METHODS: In-depth interviews and focus group discussions were conducted with community elders, health officials, tuberculosis patients and apparently healthy individuals. Data were thematically analysed using MAXQDA software. RESULTS: Participants identified diseases such as podoconiosis, leprosy, goitre and epilepsy as hereditary and perceived some as 'curses' due to generational impact and social stigma. Disease susceptibility was attributed to divine intervention or factors such as malnutrition and sanitation. Although hereditary diseases were considered unavoidable, in some cases environmental factors were acknowledged. Participants shared personal examples to demonstrate inheritance concepts. Blood held cultural significance, and concerns about its potential misuse resulted in scepticism towards giving samples. CONCLUSIONS: This study emphasizes the significance of comprehending local beliefs and perceptions and stresses the need to establish effective communication, build trust and address underlying causes of hesitancy to improve recruitment and ensure ethical conduct.
Assuntos
Elefantíase , Opinião Pública , Humanos , Idoso , Etiópia , Grupos Focais , GenômicaAssuntos
Elefantíase , Linfedema , Humanos , Elefantíase/diagnóstico , Elefantíase/etiologia , Extremidade InferiorRESUMO
Genital elephantiasis is a severe form of lymphedema of the groin. It is characterized by progressive enlargement and distortion of the genitals, presenting significant physical, psychological, and social challenges to the affected individuals. Although pharmacological treatment of filariasis is well-established in the medical field, the surgical management of genital elephantiasis can be varied and confusing. This review article provides an in-depth analysis of the etiology, classification, severity grading, and various effective surgical treatment and reconstructive modalities commonly employed by surgeons since the early twentieth century. We also discuss how a combination approach of ablation, soft tissue coverage, and lymphatic reconstruction is viable for treating genital elephantiasis. By examining the literature, we hope to provide insights into how surgery plays a role in the holistic management of genital elephantiasis.
Assuntos
Elefantíase , Doenças dos Genitais Masculinos , Linfedema , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Elefantíase/cirurgia , Elefantíase/etiologia , Linfedema/complicações , Linfedema/cirurgia , Genitália , Doenças dos Genitais Masculinos/complicações , Doenças dos Genitais Masculinos/cirurgiaRESUMO
This case report describes a woman with the appearance of elephantine skin tumors predominantly on her left foot.
Assuntos
Elefantíase , Humanos , Elefantíase/diagnóstico , Elefantíase/etiologia , Fatores de RiscoRESUMO
Penoscrotal elephantiasis (PSE) is defined as an increase, sometimes considerable, in the volume of the external genitalia, which will be responsible for an unsightly appearance, a sexological impact and a psychological harm. The cause may be primary or secondary to a parasitic disease (filarsiosis) or to intrinsic or extrinsic lymphatic obstruction. The diagnosis is essentially clinical, with penoscrotal involvement being the most frequent. The etiological research implies the realization of certain complementary examinations according to the circumstances. Surgical treatment ideally consists of excising the mass. followed by reconstruction using grafts or local flaps of healthy skin, which is an important way of restoring comfort to the patient. We report two cases of penoscrotal elephantiasis treated surgically with good functional and aesthetic results. We update, through our own experience, aspects of the diagnostic and therapeutic care of penoscrotal elephantiasis.
Assuntos
Elefantíase , Doenças dos Genitais Masculinos , Masculino , Humanos , Elefantíase/diagnóstico , Elefantíase/etiologia , Elefantíase/cirurgia , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/cirurgia , Doenças dos Genitais Masculinos/complicações , Escroto/cirurgia , Retalhos Cirúrgicos , GenitáliaRESUMO
BACKGROUND: Chronic edema as a complication of systemic diseases or infections can mimic filarial lymphedema (also known as elephantiasis) and considered so. We describe a case of chronic lymphedema that mimicked elephantiasis in a diabetic man. CASE PRESENTATION: The patient was a 70-year-old black man, bed-bound at the time of admission following a diagnosis of stroke and hypertension in the previous 5 years. He had been diabetic for 20 years with poorly controlled diabetes mellitus. He suffered recurrent bilateral lower limb skin infections for 5 years prior to admission that culminated into progressive lowerlimb edema. The infections eventually complicated into skin edema, hardening, fissuring, and hyperkeratotic plaques. The physical examination revealed Tinea pedis and bilateral non-pitting edema of lowerlimbs to the level of the knees. Investigations confirmed non-filarial lymphedema-related skin changes. The absence of the classic pebbly/cobblestone skin changes ruled out elephantiasis nostra verrucosa (ENV), with a possibility of it being in the early stages of evolution. The patient's skin fissuring and infections were successfully treated with antibiotics and antifungals while compression stockings helped to relieve the edema. CONCLUSIONS: Chronic lymphedema can complicate repeated non-filarial infections of lower limbs. Its fissures are a risk factor for cellulitis, prompting early identification and management of both infections and lymphedema to halt their vicious cycle, especially in at risk populations like diabetics.
Assuntos
Diabetes Mellitus , Elefantíase , Linfedema , Masculino , Humanos , Idoso , Elefantíase/complicações , Elefantíase/terapia , Extremidade Inferior , Linfedema/complicações , Linfedema/terapia , EdemaRESUMO
BACKGROUND: Podoconiosis (endemic non-filarial elephantiasis) is a chronic disease characterized by the development of persistent swelling of plantar foot initially; which progresses to the dorsal foot and lower leg slowly or in a number of acute episodes to reach the knee. About 4 million people are said to be affected by the disease worldwide and it is deemed a serious public health problem in at least 10 African countries including Ethiopia. Therefore this study aimed to identify the determinants of podoconiosis among residence in Machakel district. METHOD: Unmatched case control study design was conducted at Machakel district from August 30 to September 30, 2022. The sample size calculated using Epi-info software yielded 211 controls and 106 cases (317 study participants). Simple random sampling technique was used to select the cases using registration books of the district. Data were entered to Epi info version 7 and exported to SPSS version 22 for statistical analysis. Binary logistic regression was used to identify explanatory variables. RESULT: A total of 312 study participants (104 cases and 208 controls) were included giving a response rate of 98.42%. Bare foot (AOR, 5.83 [95% CI: 2.34-14.50]), female sex (AOR, 4.25 [95% CI: 2.22-8.14]), family history of podoconiosis (AOR: 3.01(95% CI: 1.41-6.42) and age group 41-60 (AOR: 5.05(95% CI: 2.35-10.83), and 61-80 AOR 15.74 95% CI: (5.56-44.55) were determinants of Podoconiosis. CONCLUSION AND RECOMMENDATION: Barefoot, sex, family history of podoconiosis and age were determinants of Podoconiosis. District health office should encourage at risk populations especially older people and individuals with family history of podoconiosis about shoe wearing practice all the time and not to expose their skin and feet.
Assuntos
Elefantíase , Humanos , Feminino , Idoso , Elefantíase/epidemiologia , Etiópia/epidemiologia , Estudos de Casos e Controles , Fatores de Risco , Perna (Membro)RESUMO
BACKGROUND: The Beach Center Family Quality of Life Scale has been developed and validated in different languages in different countries. However, this scale has not been validated in the Ethiopian Amharic language context. Therefore, this study aimed to investigate the cross-cultural validity of the Beach Center Family Quality of Life Scale, among Ethiopian families of persons affected by leprosy and podoconiosis. METHODOLOGY: We explored the semantic equivalence, internal consistency, reproducibility, floor and ceiling effects, and interpretability of the Beach Center Family Quality of Life Scale in Amharic. A cross-sectional study was conducted after the translation and back-translation of the instrument. A total of 302 adult persons affected by leprosy or podoconiosis was asked about their level of satisfaction with their family life, using the Beach Center Family Quality of Life Scale. In addition, 50 participants were re-interviewed two weeks after the initial assessment to test the reproducibility of the scale. Participants were recruited in the East Gojjam zone of Northwest Ethiopia. RESULTS: The findings of this study showed that the Beach Center Family Quality of Life Scale had high internal consistency (Cronbach's alpha of 0.913) and reproducibility (intra-class correlation coefficient of 0.857). The standard error of measurement was 3.01, which is 2.4% of the total score range. The smallest detectable change was 8.34. Confirmatory factor analysis showed adequate factor loadings and model fit indices like the original scale. The composite reliability and average variance extracted from the scale were acceptable. No floor and ceiling effects were found. CONCLUSIONS: Our findings indicate that the Amharic version of the Beach Center Family Quality of Life Scale has adequate cultural validity to assess the family quality of life in Ethiopian families of persons affected by leprosy and podoconiosis.
Assuntos
Elefantíase , Hanseníase , Adulto , Humanos , Reprodutibilidade dos Testes , Qualidade de Vida , Comparação Transcultural , Etiópia , Estudos Transversais , Inquéritos e Questionários , PsicometriaRESUMO
BACKGROUND: Podoconiosis is one of the neglected tropical diseases (NTD) with the greatest potential for elimination. Despite its public health importance, podoconiosis is a poorly understood disease which led to a widespread misconception about its cause, prevention, and treatment. Even though the exact global burden is still to be measured, it is estimated that at least 4 million people are affected with podoconiosis worldwide, of which more than 1.5 million people are in Ethiopia. The objective of this study was to identify the determinants of podoconiosis in Bensa District, Sidama Regional State, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: A community-based unmatched case-control study was used to identify the determinants of podoconiosis. The sample size was estimated using the double population proportion formula. An interviewer-administered structured questionnaire was used for data collection. Blood specimens collected from cases were tested by Filariasis Test Strip to exclude lymphatic filariasis. Data were checked for completeness, coded and entered into Epi-data Version 4.6, and exported to the SPSS version 22 software. Variables with a p<0.2 in the bivariate analysis were further analyzed using multivariable binary logistic regression. Multivariable logistic regression analysis was used to examine determinants that could be associated with podoconiosis with a 95% confidence interval. A total of 459 (153 cases and 306 controls) participants were included with a response rate of 100%. Factors such as the age of participant [AOR = 0.34, 95% CI (0.13-0.87)], being female [AOR = 2.90, 95% CI (1.40-6.10)], age at which shoe wearing started [AOR = 0.7, 95% CI (0.03-0.16)], not wearing shoe daily [AOR = 2.26, 95% CI (1.05-4.86)], wearing hard plastic shoe [AOR = 3.38, 95% CI (1.31-10.89)], and family history with a similar disease (leg swelling) [AOR = 10.2, 95% CI (3.97-26.37)] were significantly associated with the occurrence of podoconiosis. CONCLUSIONS/SIGNIFICANCE: The age of the participants, gender, the age at which shoe wearing started, type of shoe the participants' wear, frequency of shoe wearing, traveling barefoot, and family history with similar disease (leg swelling) were significantly associated with the occurrence of podoconiosis. Sidama regional health bureau along with non-governmental organizations working on the neglected tropical disease should plan modalities on awareness creation and comprehensive health education on shoe wearing and foot hygiene.
Assuntos
Filariose Linfática , Elefantíase , Humanos , Feminino , Masculino , Elefantíase/epidemiologia , Elefantíase/prevenção & controle , Estudos de Casos e Controles , Etiópia/epidemiologia , Coleta de Dados , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/prevenção & controleRESUMO
The non-filarial and non-communicable disease podoconiosis affects around 4 million people and is characterized by severe leg lymphedema accompanied with painful intermittent acute inflammatory episodes, called acute dermatolymphangioadenitis (ADLA) attacks. Risk factors have been associated with the disease but the mechanisms of pathophysiology remain uncertain. Lymphedema can lead to skin lesions, which can serve as entry points for bacteria that may cause ADLA attacks leading to progression of the lymphedema. However, the microbiome of the skin of affected legs from podoconiosis individuals remains unclear. Thus, we analysed the skin microbiome of podoconiosis legs using next generation sequencing. We revealed a positive correlation between increasing lymphedema severity and non-commensal anaerobic bacteria, especially Anaerococcus provencensis, as well as a negative correlation with the presence of Corynebacterium, a constituent of normal skin flora. Disease symptoms were generally linked to higher microbial diversity and richness, which deviated from the normal composition of the skin. These findings show an association of distinct bacterial taxa with lymphedema stages, highlighting the important role of bacteria for the pathogenesis of podoconiosis and might enable a selection of better treatment regimens to manage ADLA attacks and disease progression.