SURVEILLANCE OF A CHRONIC LIVER DISEASE OF UNIDENTIFIED CAUSE IN A RURAL SETTING OF ETHIOPIA: A CASE STUDY.

BACKGROUND: An outbreak of a chronic liver disease of unidentified cause, known as "Unidentified Liver Disease (ULD)" by local communities was first observed in a rural village in Tigray, northern-Ethiopia in 2001. Little was known about the geographical extent, trend, and epidemiology of the disease. METHODS: The Ethiopian Public Health Institute (EPHI) by then Ethiopian Health and Nutrition Research Institute (EHNRI), Centers for Disease Control and Prevention, World Health Organization, and Tigray Regional Health Bureaue established the ULD surveillance system in 2009 to characterize and monitor trends for this emerging disease and to identify cases for treatment and follow up. A large-scale official training was provided to the surveillance staff on case identification, management and reporting. In absence of a confirmatory test, the system used simple case definitions that could be applied by frontline staff with varying clinical training. To maximize resources, health extension workers already conducting household visits in affected communities identified cases and increased community awareness about the disease. A team was placed in Shire, in close proximity to the outbreak region, to provide support and collect reports from health facilities and district health offices. RESULTS: As of September 2011, a total of 1,033 cases, including 314 deaths were identified. Contamination of locally produced grains with several pyrrolizidine alkaloid producing plants was identified cause of the disease. Staff interviews identified that shortage and turnover of trained staff were major challenges. LESSONS LEARNED: Long term dedication by frontline staff, using simple case definitions to identify cases, and active collection of missing reports were critical for surveillance of this chronic non-infectious disease of unknown cause in a rural, resource-limited setting.

High Mortality from Blood Stream Infection in Addis Ababa, Ethiopia, Is Due to Antimicrobial Resistance.

BACKGROUND: Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa. METHODS: Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time. RESULTS: Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38-25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3-164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3-4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32-7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole. CONCLUSION: Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality.

Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial.

BACKGROUND: Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms.In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications. METHODS: The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years' duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level of functioning. Whether changes are maintained post intervention will also be measured (PANSS). Key assessment for the primary outcome will be conducted at the end of trial (week 12). One post-intervention assessment will be conducted 4 weeks after the end of intervention (week 16) to determine sustainability of change. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01809158.

Outbreak of epidemic dropsy in Ethiopia: the clinical and therapeutic observation.

INTRODUCTION: Epidemic dropsy results from ingestion of argemone oil contaminated food staffs. The oil from Argemone Mexican seeds contains toxic alkaloids called sanguinarine and dehydrosangunarine. These cause wide spread capillary dilatation, proliferation and leakages. This leads to oedema, hypovolemia and hypotension. OBJECTIVE: To describe the socio-demographic and clinical manifestations of the patients affected with epidemic dropsy in Tikur Anbessa specialized Hospital (TASH). METHODS: A case series study was conducted in an outbreak with unusual cases which was later diagnosed to be epidemic dropsy. Clinical evaluation of suspects was done and optimal therapy given for the complications detected and information was filled in structured format by medical residents and medial chart records review was made for occurrence of new complications in the end of 9 months. RESULTS: A total of 164 patients were seen at TASH from 26 households, in 8 sub-cities of Addis Ababa. A wide range of age group was affected with 70% from 16 to 40 years of age. There was no case among less than 5 years of age. Females were affected more than threefold as compared to males. All the patients manifested with bilateral leg swelling and pitting oedema. It was tender in 50 (30.4%) of them while 43 (26.2%) had erythema. Tachycardia was the next common manifestation occurring in 135 (82.3%), followed by cough in 123 (75%), anaemia in 59 (36%), headache in 58 (35.4%), shortness of breathing in 52 (31.2%), hair loss in 44 (26.8%) and respiratory distress in 35 (21.3%). Abdominal pain, hepatomegally, nausea and vomiting were also seen. There was abnormality in the chest X-ray of 31 (27.2%). Hair loss, tingling and burning extremities, difficulty of standing, hyperpigmentation, pruritic rash and eye symptoms were observed lately during follow up. Five of the patients died while in hospital care due to acute respiratory distress syndrome (ARDS). CONCLUSIONS: The commonest clinical manifestation in our patients is bilateral leg swelling which is similar to other outbreaks of epidemic dropsy elsewhere. The mortality rate is also comparable with other series but all cases died by ARDS in our series which is unusual in other reports. As this is the first reported epidemics in Ethiopia the findings will create awareness of clinical features of epidemic dropsy among clinicians, and therefore, helps for diagnoses of similar problems in the future.

Outbreak investigation of epidemic dropsy in Addis Ababa, Ethiopia:.

BACKGROUND: A 17 year old female patient who presented to a tertiary Hospital in Addis Ababa with bilateral painful leg swelling of two months and shortness of breath, associated with cough and haemoptysis of one week duration was reported to the Ministry of Health and the Addis Ababa Health Bureau. The condition was later detected in 18 individuals from 4 households indicating occurrence of an outbreak of unknown cause in Addis Ababa which lasted during May-July 2008. OBJECTIVE: An outbreak investigation was initiated to identify the cause and prevent further spread, morbidity and mortality. METHODS: Using semi-structured questionnaire, quantitative assessment involving individual cases and affected households was conducted to detect aetiology and risk factors. Unaffected households as well as unaffected members of affected households were also included for comparison purpose. Record review of patients visiting hospitals was also done. Data were collected through house to house visits, and using interview of cases admitted to hospital. Samples of cooking oil were collected for laboratory testing. Data analysis was done using SPSS. RESULTS: A total of 182 patients, 50 (27.5%) males and 132 (72.5%) females, were identified till the outbreak was controlled fully. Age varied from 6-90 years. Death was confirmed in 12 cases, 8 of whom were female. The majority of the patients came from the adjoining Lideta (39.0%) and Kolfe Keranyo (31.9%) subcities. History of illness ranged from less than a week to 12 weeks before presentation. Out of the 106 household members of the 24 affected households identified during the first phase of the investigation, 83 were affected. Most family members who infrequently take meals at home, and children aged 3 years and below were spared. The 21 visited affected households from Kolfe keranyo, Lideta and Bole subcities bought cooking oil produced by a firm in Lideta subcity and all had bought their last supplies in March and April 2008. Samples of cooking food oil taken from this firm and from the affected households were found to have alkaloids of Argemone Mexicana. The number of new cases dropped to zero within 6 weeks after the source was closed. CONCLUSION: The occurrence of bilateral leg swelling in more than one family member of affected households, that bought cooking oil from the same source, sparing the toddlers, and those who infrequently take meals at home, further strengthened by laboratory confirmation of presence of argemone alkaloids in the cooking oil samples taken from the affected households and the common sources led to the diagnosis of the outbreak to be epidemic dropsy.

Laboratory investigation of epidemic dropsy in Addis Ababa, Ethiopia.

BACKGROUND: Food adulteration including adulteration of edible oils may cause serious health problems. One of the most common edible adulterants is argemone oil. An outbreak of epidemic dropsy occurred in Addis Ababa during May-June, 2008. One hundred and eighty two cases were recorded with twelve confirmed deaths. Dietary history of the cases revealed that vegetable oils were the usual cooking medium. OBJECTIVE: The aim of the study was hence to investigate the causes of this outbreak. METHODS: Contaminant identification was done using standard chemical tests, complemented with TLC. Toxicity study was done using Swiss albino mice feed with contaminated and non contaminated standard diet for 30 days. RESULTS: Laboratory investigation of the edible oils has indicated that 47 of the 280 edible oils analyzed were adulterated with argemone oil. About 81% of the edible oil samples collected from Lideta sub-city were adulterated with argemone oil. Toxicological investigation of the adulterated oils also indicated typical features of argemone alkaloid poisoning in mice. CONCLUSION: Results of both laboratory analysis and toxicological studies confirmed consumption of edible oils adulterated with argemone oil as the cause of epidemic dropsy in Addis Ababa.

Epidemic dropsy: case report and the morphologic features in a patient who died at Tikur Anbessa Specialized Hospital.

Epidemic dropsy results from the consumption of edible oils adulterated with argemone mexicana oil. In a 2008 epidemic in Addis Ababa five patients died and in one of these a partial autopsy has been performed. The clinical impression of acute respiratory distress syndrome has been confirmed by the demonstration of massive diffuse alveolar damage. These features are consistent with findings reported in similar epidemics.

An outbreak of veno-occlusive liver disease in northern Ethiopia, clinical findings.

BACKGROUND: Following the emergence of an unidentified fatal disease in Tahtay Koraro, rural farmers' village in Tigray, northern Ethiopia since 2001, a team of experts from Addis Ababa University Medical Faculty was assigned in November 2005, to investigate the problem in the field. The team consisted of an Infectious disease specialist, a Gastroenterologist, an Epidemiologist, a Pathologist, and a Microbiologist. The team was also joined by a group of Tigray Regional Health Bureauprofessionals. OBJECTIVES: To investigate the nature of unidentified liver disease, identify possible cause(s) and recommend specific interventions/treatment in order to save lives and stop further spread of the disease. METHODS: Data were collected from Clinical history, clinical evaluation of the affected cases in the area, relevant laboratory investigations, and histopathologic studies. RESULTS: The team evaluated sixty one of patients in the field (37 males and 24 females) with mean age of 27 years. The disease affected both gender and all age groups. Duration of the illness ranged from 1 month to 3 years with a median of 6 months. The illness was reported to have started with abdominal cramp in 75%, febrile syndrome in 77%, and abdominal distention in 63% of the cases. This was usually followed by jaundice, bleeding tendencies, and edematous states mainly in the form of rapidly filling ascites. Majority of the patients had similarly sick family members and/or lost family member(s) due to the same illness. Moreover, laboratory, sonography, histopathological, and toxicological studies revealed VOLD due to Pyrrolizidine alkaloid (PA) toxicity as described in the other sections of the supplement. CONCLUSION: From a detailed clinical and epidemiological investigation as well as histopathological and toxicological analyses, the disease was found to be fatal toxic hepatitis (veno-occlusive liver disease (VOLD). To our knowledge, this is the first report of VOLD from Ethiopia.

Veno-occlusive liver disease: a case report.

A case of veno-occlusive liver disease (VOLD) in a 12-years old Ethiopian boy is described The salient clinical features and gross and microscopic examination of biopsy material are reviewed. Veno-occlusive disease which occurs in the West Indies, East and West Africa, and India is an acute, subacute or chronic condition that affects the central and sublobular hepatic veins. In the West Indies (1) it is related to the consumption of bush tea made from plants that contain toxic pyrrolizidine alkaloids, such as Crotalaria and Senecio (2). Hepatotoxic compounds in Crotalaria, Senecio, Heliotropium and other composite plants can also enter the diet through the contamination of cereals with weed seeds. For example 28 of 67 patients died with veno-occlusive disease in central India after consuming a local cereal, gondli contaminated with the seeds of Crotalaria (3). Heliotropium Popovii has been implicated in outbreaks in villages in northwestern Afghanistan, with high mortality (4). The primary pathological change of hepatic veno-occlusive disease is sub-endothelial edema followed by intimal growth of connective tissue, with narrowing and occlusion of the central and sub-lobular hepatic veins. Atrophy or necrosis of liver cells, with consequent fibrosis leads to gross changes similar to those seen in cardiac cirrhosis, portal hypertension results. The present report, the first of it kind in Ethiopia describes a case of veno-occlusive liver disease in a 12-year old Ethiopian boy.

Adverse drug reactions associated with antiretroviral treatment among adult Ethiopian patients in a tertiary hospital.

BACKGROUND: Adverse drug reactions (ADRs) are frequently encountered among patients taking Antiretroviral Treatment (ART). The aim of this study was to describe the type and frequency of ADRs among adult Ethiopians on ART. OBJECTIVE: to describe the type and frequency of short term adverse drug reactions among adult Ethiopian patients on ART at Tikur Anbessa teaching Hospital in Addis Ababa, Ethiopia. METHODS: From October 2008 to December 2009, 228 HIV positive patients were enrolled to a tertiary teaching hospital in Addis Ababa. Patients were closely monitored for ADRs for a median observation period of 18 weeks (79 total person-years of observation). Time-dependent occurrence of clinical adverse effects and abnormal laboratory values as defined by the AIDS Clinical Trial Group were analyzed (41). RESULTS: A total of 392 ARV drug related ADRs occurred Mild GI disturbances (36.8%) and headache (35.9%) were the most frequently reported symptoms. Thirty (7.7%) of the ADRs were severe requiring change or interruption of therapy (19 hematological and 11 hepatotoxic). Severe hematological complications were anemia (4.8%), neutropenia (2.6%) and thrombocytopenia (0.9%). Anemia occurred earl), in the first 4 weeks of ART treatment. Hepatic toxicity was also seen early but continued throughout the observation period, decreasing over time. Other ADRs encountered were grade I/II toxicities of rash, peripheral neuropathy, and metabolic disturbances. CONCLUSION AND RECOMMENDATIONS: ADRs occurred frequently in patients receiving ART. Grade III/IV toxicity that required withholding or change of treatment occurred in nearly 10% of the patients. Regular clinical, and laboratory monitoring appropriate to centers with limited resources need to be devised to monitor toxicity of ART Patient education on the easily recognizable ADRs could also reduce severe drug toxicities.

Cryptococcal meningitis in patients with acquired immunudeficiency syndrome in prehaart era at Gondar College of Medical Sciences Hospital north-west Ethiopia.

BACKGROUND: CIyptococcal meningitis is an important opportunistic funimgal infection that became very common after the era of HIV infection. OBJECTIVES: To determine the magnitude of Clyptococcal meningitis and study the clinical pattern among inpatients with HV infection at Gondar Hospital. METHODS: A descriptive study was done among ELISA confirmed admitted HIV patients. Clinically suspected cases of meningitis underwent lumbar puncture and cerebrospinal fluid analysis. The clinical profile and outcomes of the confirmed Cryptococcal meningitis cases were described. RESULTS: Among 375 HIV serology positive patients 31 were confirmed to have Cryptococcal meningitis. Their median age was 29 years (range 16-64); and 22 were males. The major manifestation at presentation included headache and fever each in 90% malaise (65%), stiffness of the neck (48%), altered Mentation (32%) and nausea and vomiting (32%), photophobia (23%) and seizure (3.6%). Median duration of illness was 16 days; ranging from 1-40 days. Temperature was above 38.4 degreees C in 80%. Meningial signs were observed in 32% altered Mentation was noted in 29% and focal neurologic deficit in 19% Cerebrospinal fluid examination revealed visually increased pressure (measured opening pressure >200 mmH2O in six patients) in 81% glucose < 50 mg/dl (50-70 mg/ dl) in 55% Protein >40 mg/dl (15-40 mg/dl) in 35% leukocytes count < 20/mm3 (poor prognostic sign) in 58% Indian ink staining detected encapsulated yeasts in 71% C. neoformans was cultivated in 90% of sample. Highest case fatality rate of the disease was observed during the pre HAART era. CONCLUSION: Cryptococcal Meningitis is common among patients with immune-suppression. It could be the initial manifestation of HIV infection and should be suspected in any potential HIV infected patient with neurological symptoms especially headache and fever. As it has highest case fatality rate, early diagnosis and prompt therapy is strongly recommended Better treatment options like boosting their immunity with HAART should also be investigated

Artemether-Lumefantrin (Coartem) and artesunate with sulfadoxine-pyrimethamine therapeutic efficacy in the treatment of uncomplicated malaria at Gilgel Gibe II (GGII) South-Western Ethiopia.

BACKGROUND: Artesunate derivative drugs are newly introduced antimalaria drugs developed in response to the increasing drug resistance malaria spread. OBJECTIVE: To determine the parasitological resistance and the clinical failure to Artemether-Lumefantrin (Coartem); and artesunate plus sulfadoxine pyrimethamine (SP) by the WHO 14 day in vivo test. METHODS: The WHO 14 day in vivo efficacy study for coartem and artesunate with sulfadoxine-pyrimethamine covered the period from Nov 28 to Dec. 26, 2006 with 141 patients of ages 2 - 35 years with uncomplicated malaria around the big hydroelectric power dam region of Gilgel Gibe II (GGII). There was close clinical follow up and included parasitic load and clearance. Packed red cell volume (Hematocrit) was measured at day 0 and 14. RESULTS: Parasitological resistance (RI, RII, RIII) to Coartem; and artesunate plus SP was not observed. There was no early as well as late clinical failure. All patients had adequate clinical response. The prevalence of malarial anemia (Hct < 33%) was 14.9% at day 0 and had decreased to 7.5% by day 14 in both groups. CONCLUSION: Coartem and artesunate with SP are highly efficacious in the treatment of uncomplicated malaria in the GGII hydroelectric dam area.

A case report of chronic tetanus.

Here, we report a case of tetanus who presented with five months of symptoms and signs suggesting the presence of unusual presentation of tetanus so called chronic tetanus. The available literature on this a typical presentation and difficulty in the diagnosis is briefly discussed.

Treatment of intestinal worms is associated with decreased HIV plasma viral load.

BACKGROUND: We have previously suggested that helminthic infections make the host more susceptible to HIV infection and enhance its progression due to the chronic immune activation they cause. OBJECTIVE: To study the effect of antihelminthic treatment on HIV plasma viral load (VL) in HIV- and helminth-infected individuals living in Ethiopia. METHODS: Fifty-six clinically asymptomatic HIV-1-infected individuals, 31 (55%) of whom were also infected with helminths, were studied. All participants received antihelminthic treatment at baseline and at 3 and 6 months. Worm egg excretion, HIV plasma VL, and T-cell subsets were determined at baseline and 6 months after treatment. RESULTS: The mean age, number of CD4 T cells, and gender distribution were similar in the helminth-infected and -noninfected groups. At baseline, HIV plasma VL was strongly correlated to the number of eggs excreted (p <.001) and was higher in individuals infected with more than one helminth (5.28 +/- 0.35 versus 4.30 +/- 1.13 log RNA copies/mL, respectively; p =.16). After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group (p =.04) CONCLUSIONS: Helminth "load" is correlated to HIV plasma VL, and successful deworming is associated with a significant decrease in HIV plasma VL. The results of the current study, if confirmed in a larger study, may have important implications for slowing disease progression and reducing risks of transmission.