Clinical features and management of a severe paradoxical reaction associated with combined treatment of Buruli ulcer and HIV co-infection.

BACKGROUND: In West and Central Africa Buruli ulcer (BU) and HIV co-infection is increasingly recognised and management of these two diseases combined is an emerging challenge for which there is little published information. In this case we present a severe paradoxical reaction occurring after commencing antibiotic treatment for BU combined with antiretroviral therapy for HIV, and describe its clinical features and management. This includes to our knowledge the first reported use of prednisolone in Africa to manage a severe paradoxical reaction related to BU treatment. CASE PRESENTATION: A 30 year old immunosuppressed HIV positive man from Cameroon developed a severe paradoxical reaction 24 days after commencing antibiotic treatment for BU and 14 days after commencing antiretroviral therapy for HIV. Oral prednisolone was successfully used to settle the reaction and prevent further tissue loss. The antiretroviral regimen was continued unchanged and the BU antibiotic treatment not prolonged beyond the recommended duration of 8 weeks. A second small local paradoxical lesion developed 8 months after starting antibiotics and settled with conservative treatment only. Complete healing of lesions occurred and there was no disease recurrence 12 months after commencement of treatment. CONCLUSIONS: Clinicians should be aware that severe paradoxical reactions can occur during the treatment of BU/HIV co-infected patients. Prednisolone was effectively and safely used to settle the reaction and minimize the secondary tissue damage.

Effectiveness of blood transfusions and risk factors for mortality in children aged from 1 month to 4 years at the Bon Marché Hospital, Bunia, Democratic Republic of the Congo.

OBJECTIVE: To assess the effectiveness of blood transfusions in a hospital of north-eastern Democratic Republic of the Congo. METHODS: Prospective study of children admitted for severe anaemia. During admission, data were collected on clinical condition and haemoglobin levels, before and after blood transfusion. A linear regression model was built to explore factors associated with haemoglobin level after transfusion. Risk factors for mortality were explored through multivariate logistic regression. RESULTS: Haemoglobin level (Hb) was below 4 g/dl in 35% (230/657), between 4 and 6 g/dl in 58% (348/657) and at least 6 g/dl in another 6% (43/657) of the transfused children. A transfusion of 15 ml/kg of whole blood increased the Hb from 4.4 to 7.8 g/dl. Haemoglobin level after transfusion was associated with baseline Hb, quantity of delivered blood and history of previous transfusions. Overall case-fatality rate was 5.6% (37/657). Risk factors for deaths were co-morbidities such as chest infection, meningitis or malnutrition, Hb ≥ 6 g/dl, impaired consciousness or jugular venous distention on admission, and provenance. CONCLUSION: Transfusion was a frequent practice, the use of which could clearly have been rationalised. While indications should be restricted, quantities of transfused blood should be adapted to needs.

Strengthening the community health program in Liberia: Lessons learned from a health system approach to inform program design and better prepare for future shocks.

BACKGROUND: Arising from the Ebola virus disease (EVD) outbreak, the 2015-2021 Investment Plan aimed to improve the health status of the Liberian population through building a resilient health system that contributes to achieving equitable health outcomes. Recognizing the significance of community participation in overcoming the EVD outbreak, strengthening community systems emerged as one of the most important strategies for bridging the gap in accessing primary health care (PHC) services. This study reviewed the community health policy development process in order to draw lessons from the health system strengthening efforts in Liberia post-EVD crisis. METHODS: A government-led health system analysis approach was applied to assess, review and revise the community health program in Liberia. The mixed method approach combines the use of an adapted tool to assess bottlenecks and solutions during workshops, a qualitative survey (key informant interviews and focus group discussions) to assess perceptions of challenges and perspectives from different stakeholders, and an inter-agency framework - a benchmarks matrix - to jointly review program implementation gaps using the evidence compiled, and identify priorities to scale up of the community program. RESULTS: Stakeholders identified key health system challenges and proposed policy and programmatic shifts to institutionalize a standardized community health program with fit for purpose and incentivized community health assistants to provide PHC services to the targeted populations. The community health program in Liberia is currently at the phase of implementation and requires strengthened leadership, local capacities, and resources for sustainability. Lessons learned from this review included the importance of: establishing a coordination mechanism and leveraging partnership support; using a systems approach to better inform policy shifts; strengthening community engagement; and conducting evidence-based planning to inform policy-makers. CONCLUSIONS: This article contributes toward the existing body of knowledge about policy development processes and reforms on community health in Liberia, and most likely other African settings with weak health systems. Community-based systems will play an even bigger role as we move toward building resilience for future shocks and strengthening PHC, which will require that communities be viewed as actors in the health system rather than just clients of health services.

Differential Diagnosis of Skin Ulcers in a Mycobacterium ulcerans Endemic Area: Data from a Prospective Study in Cameroon.

BACKGROUND: Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. METHOD: We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. RESULTS/ DISCUSSION: Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p<0.001). Children had more superficial bacterial infections (24.3%) and osteomyelitis (11.4%). CONCLUSION: We described differential diagnosis of skin lesions in a BU endemic area, stratifying results by age and HIV-status.

The "Buruli Score": Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon.

BACKGROUND: Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. METHODODOLOGY/PRINCIPAL FINDINGS: Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82-0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0-98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2-84.7). Patients with intermediate BU probability needed to be tested by PCR. CONCLUSIONS/SIGNIFICANCE: We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use.

The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa.

Despite great advances in the diagnosis and treatment of Buruli ulcer, it is one of the least studied major neglected tropical diseases. In Africa, major constraints in the management of Buruli ulcer relate to diagnosis and treatment, and accessibility, feasibility, and delivery of services. In this Personal View, we outline key areas for clinical, diagnostic, and operational research on this disease in Africa and propose a research agenda that aims to advance the management of Buruli ulcer in Africa. A model of care is needed to increase early case detection, to diagnose the disease accurately, to simplify and improve treatment, to reduce side-effects of treatment, to deal with populations with HIV and tuberculosis appropriately, to decentralise care, and to scale up coverage in populations at risk. This approach will require commitment and support to strategically implement research by national Buruli ulcer programmes and international technical and donor organisations, combined with adaptations in programme design and advocacy. A critical next step is to build consensus for a research agenda with WHO and relevant groups experienced in Buruli ulcer care or related diseases, and we call on on them to help to turn this agenda into reality.