The NLR SkinApp: Testing a Supporting mHealth Tool for Frontline Health Workers Performing Skin Screening in Ethiopia and Tanzania.

Background: The prevalence of skin diseases such as leprosy, and limited dermatological knowledge among frontline health workers (FHWs) in rural areas of Sub-Saharan Africa, led to the development of the NLR SkinApp: a mobile application (app) that supports FHWs to promptly diagnose and treat, or suspect and refer patients with skin diseases. The app includes common skin diseases, neglected tropical skin diseases (skin NTDs) such as leprosy, and HIV/AIDS-related skin conditions. This study aimed to test the supporting role of the NLR SkinApp by examining the diagnostic accuracy of its third edition. Methods: A cross-sectional study was conducted in East Hararghe, Ethiopia, as well as the Mwanza and Morogoro region, Tanzania, in 2018-2019. Diagnostic accuracy was measured against a diagnosis confirmed by two dermatologists/dermatological medical experts (reference standard) in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The potential negative effect of an incorrect management recommendation was expressed on a scale of one to four. Results: A total of 443 patients with suspected skin conditions were included. The FHWs using the NLR SkinApp diagnosed 45% of the patients accurately. The values of the sensitivity of the FHWs using the NLR SkinApp in determining the correct diagnosis ranged from 23% for HIV/AIDS-related skin conditions to 76.9% for eczema, and the specificity from 69.6% for eczema to 99.3% for tinea capitis/corporis. The inter-rater reliability among the FHWs for the diagnoses made, expressed as the percent agreement, was 58% compared to 96% among the dermatologists. Of the management recommendations given on the basis of incorrect diagnoses, around one-third could have a potential negative effect. Conclusions: The results for diagnosing eczema are encouraging, demonstrating the potential contribution of the NLR SkinApp to dermatological and leprosy care by FHWs. Further studies with a bigger sample size and comparing FHWs with and without using the NLR SkinApp are needed to obtain a better understanding of the added value of the NLR SkinApp as a mobile health (mHealth) tool in supporting FHWs to diagnose and treat skin diseases.

Fingerstick test quantifying humoral and cellular biomarkers indicative for M. leprae infection.

OBJECTIVES: New user-friendly diagnostic tests for detection of individuals infected by Mycobacterium leprae (M. leprae), the causative pathogen of leprosy, can help guide therapeutic and prophylactic treatment, thus positively contributing to clinical outcome and reduction of transmission. To facilitate point-of-care testing without the presence of phlebotomists, the use of fingerstick blood (FSB) rather than whole blood-derived serum is preferred. This study is a first proof-of-principle validating that previously described rapid serum tests detecting antibodies and cytokines can also be used with FSB. METHODS: Quantitative detection of previously identified biomarkers for leprosy and M. leprae infection, anti-M. leprae PGL-I IgM antibodies (αPGL-I), IP-10 and CRP, was performed with lateral flow (LF) strips utilizing luminescent up-converting reporter particles (UCP) and a portable reader generating unbiased read-outs. Precise amounts of FSB samples were collected using disposable heparinized capillaries. Biomarker levels in paired FSB and serum samples were determined using UCP-LF test strips for leprosy patients and controls in Bangladesh, Brazil, South-Africa and the Netherlands. RESULTS: Correlations between serum and FSB from the same individuals for αPGL-I, CRP and IP-10 were highly significant (p < .0001) even after FSB samples had been frozen. The αPGL-I FSB test was able to correctly identify all multibacillary leprosy patients presenting a good quantitative correlation with the bacterial index. CONCLUSIONS: Reader-assisted, quantitative UCP-LF tests for the detection of humoral and cellular biomarkers for M. leprae infection, are compatible with FSB. This allows near-patient testing for M. leprae infection and immunomonitoring of treatment without highly trained staff. On site availability of test-result concedes immediate initiation of appropriate counselling and treatment. Alternatively, the UCP-LF format allows frozen storage of FSB samples compatible with deferred testing in central laboratories.

The Development of a Mobile Application to Support Peripheral Health Workers to Diagnose and Treat People with Skin Diseases in Resource-Poor Settings.

The high prevalence of skin diseases in resource-poor settings, where health workers with sufficient knowledge of skin diseases are scarce, calls for innovative measures. Timely diagnosis and treatment of skin diseases, especially neglected tropical diseases (NTDs) that manifest with skin lesions, such as leprosy, is crucial to prevent disabilities as well as psychological and socioeconomic problems. Innovative technological methods like telemedicine and mobile health (mHealth) can help to bridge the gap between the burden of skin diseases and the lack of capable staff in resource-poor settings by bringing essential health services from central level closer to peripheral levels. Netherlands Leprosy Relief (NLR) has developed a mobile phone application called the 'SkinApp', which aims to support peripheral health workers to recognize the early signs and symptoms of skin diseases, including skin NTDs, and to start treatment promptly or refer for more advanced diagnostic testing or disease management when needed. Further research is needed to determine how greatly mHealth in general and the SkinApp in particular can contribute to improved health outcomes, efficiency, and cost-effectiveness.

Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia.

BACKGROUND: The clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R). METHODS: History or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants. RESULTS: There are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018). CONCLUSIONS: Our results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions.

Leprosy type 1 reaction (formerly reversal reaction).

Nerve damage leading to impairment and permanent disability is the major problem in the course of a leprosy infection. Most of the damage occurs during two types of leprosy reactions, type 1 reaction (T1R) and type 2 reaction (T2R). Timely and adequate treatment may prevent this damage. Particular T1R reactions, however, are often diagnosed too late and are even missed. Clinical symptoms and warning signs are therefore covered, as are the immunology and pathophysiology of nerve damage. The differences between upgrading and downgrading, old terms but still relevant, are explained. Methods to detect reactions and to monitor their treatment are given. Triggering factors, the mechanisms of the reactions, including autoimmunity, and the presence of physical compression are discussed. Treatment over the years is placed in its context, and based on this information a treatment schedule is recommended.

Longitudinal immune responses and gene expression profiles in type 1 leprosy reactions.

PURPOSE: Leprosy, a chronic disease initiated by Mycobacterium leprae, is often complicated by acute inflammatory reactions. Although such episodes occur in at least 50% of all leprosy patients and may cause irreversible nerve damage, no laboratory tests are available for early diagnosis or prediction of reactions. Since immune- and genetic host factors are critical in leprosy reactions, we hypothesize that identification of host-derived biomarkers correlated to leprosy reactions can provide the basis for new tests to facilitate timely diagnosis and treatment thereby helping to prevent tissue damage. METHODS: The longitudinal host response of a leprosy patient, who was affected by a type 1 reaction (T1R) after MDT-treatment, was studied in unprecedented detail, measuring cellular and humoral immunity and gene expression profiles to identify biomarkers specific for T1R. RESULTS: Cytokine analysis in response to M. leprae revealed increased production of IFN-γ, IP-10, CXCL9, IL-17A and VEGF at diagnosis of T1R compared to before T1R, whereas a simultaneous decrease in IL-10 and G-CSF was observed at T1R. Cytokines shifts coincided with a reduction in known regulatory CD39(+)CCL4(+) and CD25(high) T-cell subsets. Moreover, RNA expression profiles revealed that IFN-induced genes, (V)EGF, and genes associated with cytotoxic T-cell responses (GNLY, GZMA/B, PRF1) were upregulated during T1R, whereas expression of T-cell regulation-associated genes were decreased. CONCLUSIONS: These data show that increased inflammation, vasculoneogenesis and cytotoxicity, perturbed T-cell regulation as well as IFN-induced genes play an important role in T1R and provide potential T1R-specific host biomarkers.