Publications by authors named "John Musuku"

14 Publications

  • Page 1 of 1

Ketogenic diet in Zambia: Managing drug-resistant epilepsy in a low and middle income country.

Epilepsy Behav Rep 2020 3;14:100380. Epub 2020 Jul 3.

Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.

Globally, drug-resistant epilepsy affects one third of people living with epilepsy. With limitations in treatment options for refractory epilepsy in resource-limited regions, ketogenic diet therapy is an important option to consider. Utilizing the 2015 International League Against Epilepsy recommended minimum requirements for ketogenic diet therapy, three male children with refractory epilepsy, aged 2.5, 6.5 and 10 years, were initiated on the classical ketogenic diet using locally available food in August 2017 at University Teaching Hospitals-Children's Hospital in Lusaka, Zambia, through partnership with the Epilepsy Program at Boston Children's Hospital in the United States. Following successful initiation in all three children, the diet was discontinued in the 10-year-old due to difficulties complying with the diet. The youngest child demonstrated an over 50% seizure reduction and gained developmental milestones. The third child achieved seizure freedom and showed marked improvement in behaviour. This pilot demonstrates the feasibility of ketogenic diet as an important therapeutic option for refractory epilepsy in Zambia. Given the limitations in treatment choices and medication accessibility, dietary therapy offers an alternative management strategy in our setting. Collaboration with an established ketogenic diet centre contributes to a successful program.
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http://dx.doi.org/10.1016/j.ebr.2020.100380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393450PMC
July 2020

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

Am Heart J 2020 07 25;225:69-77. Epub 2020 Mar 25.

University Teaching Hospital of Kigali, Rwanda.

Background: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need.

Methods: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm, left atrial spontaneous echo-contrast or thrombus, or a CHADSVASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD.

Conclusion: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.
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http://dx.doi.org/10.1016/j.ahj.2020.03.018DOI Listing
July 2020

Use of broad consent and related procedures in genomics research: Perspectives from research participants in the Genetics of Rheumatic Heart Disease (RHDGen) study in a University Teaching Hospital in Zambia.

Glob Bioeth 2019 Mar 24;31(1):184-199. Epub 2019 Mar 24.

Department of Medicine, University of Cape Town, Cape Town, South Africa.

The use of broad consent for genomics research raises important ethical questions for the conduct of genomics research, including relating to its acceptability to research participants and comprehension of difficult scientific concepts. To explore these and other challenges, we conducted a study using qualitative methods with participants enrolled in an H3Africa Rheumatic Heart Disease genomics study (the RHDGen network) in Zambia to explore their views on broad consent, sample and data sharing and secondary use. In-depth interviews were conducted with RHDGen participants ( = 18), study staff ( = 5) and with individuals who refused to participate ( = 3). In general, broad consent was seen to be reasonable if reasons for storing the samples for future research use were disclosed. Some felt that broad consent should be restricted by specifying planned future studies and that secondary research should ideally relate to original disease for which samples were collected. A few participants felt that broad consent would delay the return of research results to participants. This study echoes findings in other similar studies in other parts of the continent that suggested that broad consent could be an acceptable consent model in Africa if careful thought is given to restrictions on re-use.
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http://dx.doi.org/10.1080/11287462.2019.1592868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734073PMC
March 2019

Prevalence of rheumatic heart disease in Zambian school children.

BMC Cardiovasc Disord 2018 07 3;18(1):135. Epub 2018 Jul 3.

Department of Paediatrics, Red Cross War Memorials Children's Hospital, Cape Town, South Africa.

Background: The large global burden of rheumatic heart disease (RHD) has come to light in recent years following robust epidemiologic studies. As an operational research component of a broad program aimed at primary and secondary prevention of RHD, we sought to determine the current prevalence of RHD in the country's capital, Lusaka, using a modern imaging-based screening methodology. In addition, we wished to evaluate the practicality of training local radiographers in echocardiography screening methods.

Methods: Echocardiography was conducted on a random sample of students in 15 schools utilizing a previously validated, abbreviated screening protocol. Through a task-shifting scheme, and in the spirit of capacity-building to enhance local diagnostic and research skills, general radiographers based at Lusaka University Teaching Hospital (UTH) were newly trained to use portable echocardiography devices. Students deemed as screen-positive were referred for comprehensive echocardiography and clinical examination at UTH. Cardiac abnormalities were classified according to standard World Heart Federation criteria.

Results: Of 1102 students that were consented and screened, 53 students were referred for confirmatory echocardiography. Three students had definite RHD, 10 had borderline RHD, 29 were normal, and 11 students were lost to follow-up. The rates of definite, borderline, and total RHD were 2.7 per 1000, 9.1 per 1000, and 11.8 per 1000, respectively. Anterior mitral valve leaflet thickening and chordal thickening were the most common morphological defects. The pairwise kappa test showed fair agreement between the local radiographers and an echocardiographer quality assurance specialist.

Conclusion: The prevalence of asymptomatic RHD in urban communities in Zambia is within the range of results reported in other sub-Saharan African countries using the WHF criteria. Task-shifting local radiographers to conduct echocardiography was feasible. The results of this study will be used to inform ongoing efforts in Zambia to control and eventually eliminate RHD.

Trial Registration: The study was registered on clinicaltrials.gov ( #NCT02661763 ).
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http://dx.doi.org/10.1186/s12872-018-0871-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029054PMC
July 2018

A programme to increase appropriate usage of benzathine penicillin for management of streptococcal pharyngitis and rheumatic heart disease in Zambia.

Cardiovasc J Afr 2017 Jul/Aug;28(4):242-247

University Teaching Hospital, Lusaka, Zambia.

Rheumatic heart disease is highly prevalent and associated with substantial morbidity and mortality in many resource-poor areas of the world, including sub-Saharan Africa. Primary and secondary prophylaxis with penicillin has been shown to significantly improve outcomes and is recognised to be the standard of care, with intra-muscular benzathine penicillin G recommended as the preferred agent by many technical experts. However, ensuring compliance with therapy has proven to be challenging. As part of a public-private partnership initiative in Zambia, we conducted an educational and access-to-medicine programme aimed at increasing appropriate use of benzathine penicillin for the prevention and management of rheumatic heart disease, according to national guidelines. The programme was informed early on by identification of potential barriers to the administration of injectable penicillin, which included concern by health workers about allergic events. We describe this programme and report initial signs of success, as indicated by increased use of benzathine penicillin. We propose that a similar approach may have benefits in rheumatic heart disease programmes in other endemic regions.
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http://dx.doi.org/10.5830/CVJA-2017-002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642026PMC
June 2018

Epidemiology of pharyngitis as reported by Zambian school children and their families: implications for demand-side interventions to prevent rheumatic heart disease.

BMC Infect Dis 2017 07 6;17(1):473. Epub 2017 Jul 6.

Department of Paediatrics, Red Cross War Memorials Children's Hospital, University of Cape Town, Cape Town, South Africa.

Background: Prompt and appropriate treatment of streptococcal pharyngitis decreases the risk of acute rheumatic fever and rheumatic heart disease (RHD). Understanding public perceptions and behaviors related to sore throat is fundamental to inform health programs aimed at eliminating new cases of RHD in endemic regions. We sought to describe the epidemiology of pediatric pharyngitis and its treatment, as reported by children and their parents or guardians in Lusaka, Zambia.

Methods: This was a cross-sectional investigation using interviews and written surveys, nested in a school-based RHD prevalence study. Students and their parents were asked to report number of sore throats in the previous 12 months, treatment received, and type and place of treatment. A focused history and physical examination to detect pharyngitis was conducted and children were referred for follow-up as indicated.

Results: A total of 3462 students from 47 schools participated in the study, along with their parents or guardians. Six hundred and fifty eight (19%) parents/guardians reported their child had at least one sore throat in the previous year, and 835 (24%) of students reported at least one sore throat in the same time period. Girls were reported to have pharyngitis 50% more often than boys, and also made up two-thirds of the total students treated. Approximately two-thirds of children who had at least one episode of pharyngitis during the previous year were also reported to have received some form of treatment. The majority of treatments were received in government clinics (36.6%) and at home (26.3%). Half of treatments included an antibiotic. Nineteen students (0.5%) had clinically-apparent pharyngitis at screening.

Conclusion: Pharyngitis is common among school-aged children and adolescents in Zambia, with females reporting significantly more sore throat episodes than males. Parents/guardians have variable knowledge about the frequency of sore throat in their children, and management of pharyngitis may be suboptimal for many children since more than a quarter were reported to have received treatment without skilled assessment. These results provide insight into current perceptions and practices related to sore throat in Zambia and will be used to design public awareness activities aimed at reducing RHD.
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http://dx.doi.org/10.1186/s12879-017-2563-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501010PMC
July 2017

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

Circulation 2016 Nov 4;134(19):1456-1466. Epub 2016 Oct 4.

From Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, South Africa (L.Z., M.E.E., B.C., R.D., V.F., B.M.M.); Division of Paediatric Cardiology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa (L.Z., C.H.-H.); Department of Cardiology, All India Institute of Medical Sciences, New Delhi (G.K.); Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada (S.R., P.M., S.I., K.T., S.Y.); Department of Statistical Sciences, University of Cape Town, South Africa (K.M.); Department of Surgery, School of Medicine, College of Health Sciences, University of Nairobi, Kenya (S.O.); Cardiology Unit, Department of Medicine, Kenyatta National Teaching and Referral Hospital, Nairobi, Kenya (B.G.); Cardiology Unit, Department of Medicine, Mulago Hospital, Kampala, Uganda (C.M.); Uganda Heart Institute, Kampala (E.O., P.L.); Faculty of Medicine & Surgery, University of Sana'a, Al-Thawrah Cardiac Center, Yemen (M.M.A.-K.); Paediatric Cardiology Service, Windhoek Central Hospital, Namibia (C.H.-H.); Department of Paediatrics, Division of Paediatric Cardiology, Faculty of Medicine, Cairo University Children's Hospital, Egypt (S.S.S.); Department of Paediatrics and Child Health, Jimma University Hospital, Ethiopia (A.H., W.D.); Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia (D.Y.G., S.G.A., A.G.D., B.A.S., D.M.B.); Cardiothoracic Surgery Department, Al Shaab Teaching Hospital and Faculty of Medicine, Alzaiem Alazhari University, Khartoum, Sudan (A.E., A.S.I.); University Teaching Hospital, Department of Paediatrics and Child Health, University of Zambia, Lusaka (J.M.); Departments of Paediatrics and Medicine, Jos University Teaching Hospital, Nigeria (F.B.-T., C.C.Y., G.A.A., O.I., B.O.); Department of Paediatrics and Child Health, University of Limpopo, Polokwane, South Africa (C.S.); Department of Internal Medicine, University of Limpopo, Polokwane, South Africa (R.M.); Faculty of Medicine, Benha University, Cairo, Egypt (A.A.F.); Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (N.K.); Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique (A.D.); Department of Medicine, Bayero University and Aminu Kano Teaching Hospital, Nigeria (M.U.S.); Division of Cardiology, Department of Medicine, University College Hospital, Ibadan, Nigeria (O.S.O., A.M.A.); Nigeria Ministry of Health, Umuahia, Abia State (O.S.O.); Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria (O.S.O., T.O.); Ahmed Gasim Teaching Hospital, Khartoum, Sudan (H.H.M.E.); Instituto Nacional de Saúde and Eduardo Mondlane University, Maputo, Mozambique (A.O.M.); Department of Cardiology, Dr. George Mukhari Hospital and Sefako Makgatho Health Sciences University, Tshwane, South Africa (P.M.); Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Nigeria (D.O.); and Paediatric Cardiology Unit, Department of Paediatrics, King Faisal Hospital, Kigali, Rwanda (J.M.).

Background: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia.

Methods: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis.

Results: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries.

Conclusions: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024769DOI Listing
November 2016

Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué.

Cardiovasc J Afr 2016 May/Jun 23;27(3):184-187. Epub 2016 Jan 12.

University Teaching Hospital, Zambia.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organisations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communiqué has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime.
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http://dx.doi.org/10.5830/CVJA-2015-090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125265PMC
February 2017

Improving paediatric asthma care in Zambia.

Bull World Health Organ 2015 Oct 19;93(10):732-736. Epub 2015 Aug 19.

Novartis Institutes for BioMedical Research, Cambridge, United States of America .

Problem: In 2008, the prevalence of paediatric asthma in Zambia was unknown and the national treatment guideline was outdated.

Approach: We created an international partnership between Zambian clinicians, the Zambian Government and a pharmaceutical company to address shortcomings in asthma treatment. We did two studies, one to estimate prevalence in the capital of Lusaka and one to assess attitudes and practices of patients. Based on the information obtained, we educated health workers and the public. The information from the studies was also used to modernize government policy for paediatric asthma management.

Local Setting: The health-care system in Zambia is primarily focused on acute care delivery with a focus on infectious diseases. Comprehensive services for noncommunicable diseases are lacking. Asthma management relies on treatment of acute exacerbations instead of disease control.

Relevant Changes: Seven percent of children surveyed had asthma (255/3911). Of the 120 patients interviewed, most (82/120, 68%) used oral short-acting β-agonists for symptom control; almost half (59/120, 49%) did not think the symptoms were preventable and 43% (52/120) thought inhalers were addictive. These misconceptions informed broad-based educational programmes. We used a train-the-trainer model to educate health-care workers and ran public awareness campaigns. Access to inhalers was increased and the Zambian standard treatment guideline for paediatric asthma was revised to include steroid inhalers as a control treatment.

Lessons Learnt: Joint activities were required to change paediatric asthma care in Zambia. Success will depend on local sustainability, and it may be necessary to shift resources to mirror the disease burden.
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http://dx.doi.org/10.2471/BLT.14.144071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645426PMC
October 2015

An open-access, mobile compatible, electronic patient register for rheumatic heart disease ('eRegister') based on the World Heart Federation's framework for patient registers.

Cardiovasc J Afr 2015 Nov-Dec;26(6):227-33. Epub 2015 Oct 6.

Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.

Background: Rheumatic heart disease (RHD) remains a major disease burden in low-resource settings globally. Patient registers have long been recognised to be an essential instrument in RHD control and elimination programmes, yet to date rely heavily on paper-based data collection and non-networked data-management systems, which limit their functionality.

Objectives: To assess the feasibility and potential benefits of producing an electronic RHD patient register.

Methods: We developed an eRegister based on the World Heart Federation's framework for RHD patient registers using CommCare, an open-source, cloud-based software for health programmes that supports the development of customised data capture using mobile devices.

Results: The resulting eRegistry application allows for simultaneous data collection and entry by field workers using mobile devices, and by providers using computer terminals in clinics and hospitals. Data are extracted from CommCare and are securely uploaded into a cloud-based database that matches the criteria established by the WHF framework. The application can easily be tailored to local needs by modifying existing variables or adding new ones. Compared with traditional paper-based data-collection systems, the eRegister reduces the risk of data error, synchronises in real-time, improves clinical operations and supports management of field team operations.

Conclusions: The user-friendly eRegister is a low-cost, mobile, compatible platform for RHD treatment and prevention programmes based on materials sanctioned by the World Heart Federation. Readily adaptable to local needs, this paperless RHD patient register program presents many practical benefits.
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http://dx.doi.org/10.5830/CVJA-2015-058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780020PMC
September 2016

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).

Eur Heart J 2015 May 25;36(18):1115-22a. Epub 2014 Nov 25.

Department of Paediatrics, Jos University Teaching Hospital, Jos, Nigeria.

Aims: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment.

Methods And Results: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries.

Conclusion: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.
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http://dx.doi.org/10.1093/eurheartj/ehu449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422972PMC
May 2015

Congenital trypanosomiasis.

J Trop Pediatr 2004 Dec;50(6):377-8

Department of Paediatrics and Child Health, University Teaching Hospital, Lusaka, Zambia.

The last successfully treated case of congenital trypanosomiasis in Zambia was in October 1978, with detailed analysis of immunoglobulins, illustrating the waning of blood and serum levels of IgA, IgG, and IgM during treatment, up to 99 days after treatment. Twenty-five years later, we report on a case of congenital trypanosomiasis. The disease is now rare and can be missed or dismissed as retroviral disease, particularly in adults. The main unusual symptoms were the prolonged intermittent convulsions in an otherwise well infant. Management of the disease is now more interdisciplinary, resources for laboratory support are fewer, lumbar puncture is more relevant, and antitrypanosomal drugs are more difficult to obtain. The mother died within one week of hospitalization and the infant initially responded to three doses of suramin and 3 weeks of melsopropol. Convulsions ceased during the second round of melsopropol. Unfortunately, the infant died of nosocomial infection.
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http://dx.doi.org/10.1093/tropej/50.6.377DOI Listing
December 2004

Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial.

Lancet 2002 Nov;360(9343):1375-80

Department of Paediatrics, University of Zambia School of Medicine, Lusaka, Zambia.

Background: Cryptosporidiosis in children in developing countries causes persistent diarrhoea and malnutrition and is associated with increased mortality, but there is no effective treatment. We aimed to assess the effect of nitazoxanide-a new broad-spectrum antiparasitic drug-on morbidity and mortality in Zambian children with diarrhoea due to Cryptosporidium parvum.

Methods: Children with cryptosporidial diarrhoea who were admitted to the University Teaching Hospital, Lusaka, Zambia, between November, 2000, and July, 2001, and whose parents consented to their having an HIV test were randomly assigned nitazoxanide (100 mg twice daily orally for 3 days) or placebo. The primary endpoint was clinical response on day 7 after the start of treatment. Secondary endpoints included parasitological response by day 10 and mortality at day 8. Analysis was by intention to treat, with exclusion of patients subsequently found to be negative for C parvum or co-infected at baseline. The trial was stratified by HIV serology.

Findings: 50 HIV-seropositive and 50 HIV-seronegative children were recruited for the study, four of whom were subsequently excluded. In HIV-seronegative children, diarrhoea resolved in 14 (56%) of 25 receiving nitazoxanide and 5 (23%) of 22 receiving placebo (difference 33%, 95% CI 7-59; p=0.037). C parvum was eradicated from stool in 13 (52%) of 25 receiving nitazoxanide and three (14%) of 22 receiving placebo (38%, 95% CI 14-63; p=0.007). Four children (18%) of 22 in the placebo group had died by day 8, compared with none of 25 in the nitazoxanide group (-18%, -34 to 2; p=0.041). HIV-seropositive children did not benefit from nitazoxanide. Nitazoxanide was not significantly associated with adverse events in either stratum.

Interpretation: A 3-day course of nitazoxanide significantly improved the resolution of diarrhoea, parasitological eradication, and mortality in HIV-seronegative, but not HIV-seropositive, children.
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http://dx.doi.org/10.1016/S0140-6736(02)11401-2DOI Listing
November 2002