Isaac I. Bogoch

Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial

BACKGROUND Existing anthelmintic drugs (eg, albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. METHODS In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6-14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. FINDINGS We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6-77·4]; egg reduction 99·2%, 98·7-99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0-36·0]; egg reduction 94·5%, 91·7-96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1-13·8]; egg reduction 58·5%, 45·2-70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1-13·8; egg reduction 51·6%, 35·0-65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura. Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. FUNDING Medicor Foundation and Swiss National Science Foundation.

Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide

BackgroundPathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce.MethodsWe collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs).ResultsAlmost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli.ConclusionsIntestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects.

Reversible dementia in a patient with central nervous system escape of human immunodeficiency virus

HIV-associated neurocognitive disorders (HAND) are a group of conditions ranging from asymptomatic neurocognitive impairment to disabling dementia. The clinical spectrum and pathogenesis of these disorders is changing in the era of highly active antiretroviral therapy (HAART). High levels of HIV may exist in the cerebrospinal fluid (CSF) of some patients despite suppression of serum viral loads by HAART. We report a case of a 51-year-old male with profound levels of HIV in the CSF despite low serum levels. Adjusting his HAART regimen based on HIV genotype susceptibility data and a CNS Penetrating Effectiveness (CPE) score resulted in a dramatic improvement in cognitive function. Progressive dementia in this context is a rare but emerging trend and may be reversible.

Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults

The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV‐infected individuals during the antiretroviral (ARV) era in a nontuberculosis endemic setting.

Acute lower motor neuron syndrome and spinal cord gray matter hyperintensities in HIV infection

Objective: To describe a novel manifestation of lower motor neuron disease in patients with well-controlled HIV infection. Methods: A retrospective study was performed to identify HIV-positive individuals with acute, painful lower motor neuron diseases. Results: Six patients were identified with HIV and lower motor neuron disease. Two patients met the inclusion criteria of well-controlled, chronic HIV infection and an acute, painful, unilateral lower motor neuron paralytic syndrome affecting the distal portion of the upper limb. These patients had segmental T2-hyperintense lesions in the central gray matter of the cervical spinal cord on MRI. One patient stabilized and the second patient improved with immunomodulatory therapy. Conclusions: This newly described syndrome expands the clinical spectrum of lower motor neuron diseases in HIV.

Diagnosis of influenza from lower respiratory tract sampling after negative upper respiratory tract sampling

In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses of influenza were made solely by lower respiratory sampling in 6.9% of cases, as traditional upper respiratory tract tests were negative, indeterminate or not performed. Clinical features of these cases are presented. Clinicians should consider lower respiratory tract sampling in select cases of influenza-like illness for diagnosis.

Scope and Limits of an Anamnestic Questionnaire in a Control-Induced Low-Endemicity Helminthiasis Setting in South-Central Côte d’Ivoire

Background Schistosomiasis and soil-transmitted helminthiasis are two high-burden neglected tropical diseases. In highly endemic areas, control efforts emphasize preventive chemotherapy. However, as morbidity, infection, and transmission begin to decrease, more targeted treatment is likely to become more cost-effective, provided that comparatively cheap diagnostic methods with reasonable accuracy are available. Methodology Adults were administered an anamnestic questionnaire in mid-2010 during a cross-sectional epidemiological survey in the Taabo health demographic surveillance system in south-central Côte d’Ivoire. Questions pertaining to risk factors and signs and symptoms for schistosomiasis and soil-transmitted helminthiasis were included. The individuals’ helminth infection status and their belonging to three different anthelmintic treatment groups were compared with the questionnaire results (i) to inform the local health authorities about the epidemiological and clinical footprint of locally prevailing helminthiases, and (ii) to explore the scope and limits of an anamnestic questionnaire as monitoring tool, which eventually could help guiding the control of neglected tropical diseases in control-induced low-endemicity settings. Principal Findings Our study sample consisted of 195 adults (101 males, 94 females). We found prevalences of hookworm, Trichuris trichiura, Schistosoma haematobium, and Schistosoma mansoni of 39.0%, 2.7%, 2.1%, and 2.1%, respectively. No Ascaris lumbricoides infection was found. Helminth infection intensities were generally very low. Seven, 74 and 79 participants belonged to three different treatment groups. Multivariable logistic regression models revealed statistically significant (p<0.05) associations between some risk factors, signs, and symptoms, and the different helminth infections and treatment groups. However, the risk factors, signs, and symptoms showed weak diagnostic properties. Conclusions/Significance The generally low prevalence and intensity of helminth infection in this part of south-central Côte d’Ivoire indicates that recent control efforts have turned our study area into a low endemicity setting. Our anamnestic questionnaire had low sensitivity and specificity to identify infected individuals or treatment groups.

Web-based blog supplement to evidence-based physical examination teaching

in clinical practice and examinations). The Game has significantly altered staff perceptions of students and students’ perceptions of themselves; student comments include: (i) ‘I am a doctor, not just a medical student’; (ii) ‘I enjoy teaching and am a good teacher and role model’, and (iii) ‘I can mentor students by providing sound practical advice’. Further detailed evaluation and large-scale implementation of The Game in all medical clerkships will commence in 2012.

Severe Babesiosis in a Patient Treated With a Tumor Necrosis Factor α Antagonist

To the Editor—A 57-year-old woman from Cape Cod presented to our facility with fever and a syncopal episode. She reported 1 week of fatigue before her evaluation. On examination, she was febrile (38.6 C) but otherwise appeared well, with a positive Castell’s sign and palpable spleen tip. Her medical history was significant for Crohn’s disease treated with infliximab, with the most recent dose administered 6 weeks before presentation. She did not report smoking or alcohol consumption, denied any travel history, and worked in a local office. Blood work on admission revealed a white blood cell count of 6.8 3 10/lL with a normal differential, a hemoglobin level of 11.5 g/dL, a hematocrit of 34.8%, and a platelet count of 88 3 10/lL. The patient’s serum lactate dehydrogenase level was elevated (659 U/L), her creatinine level was normal (0.81 mg/dL), and her aspartate aminotransferase and alanine aminotransferase levels were slightly elevated (54 and 39 U/L, respectively). Intraerythrocytic parasites were visualized on a blood film and confirmed via light microscopy as babesia with 14.1% parasitemia. The patient was initially treated with azithromycin (500 mg daily) and atovaquone (750 mg twice daily) for babesiosis, in addition to empiric therapy with doxycycline (100 mg twice daily) for possible coinfection with Borrelia, Ehrlichia, and Anaplasma. Doxycycline was discontinued on hospital day 2, after results were negative for Ehrlichia (polymerase chain reaction) and Borrelia (serology). The patient appeared well despite parasitemia of 15% for 4 days, and her treatment was briefly switched to quinine and clindamycin (650 and 600 mg, respectively, each 3 times daily on hospital day 4). Atovaquone and azithromycin treatment were restarted on hospital day 5, when her parasitemia declined to 10%. Parasitemia was undetectable by microscopy on hospital day 7. The patient was treated for 2 additional weeks with atovaquone and azithromycin after her parasitemia became undetectable, for a total of 3 weeks of therapy. She was well at follow-up appointments 3 and 12 weeks after hospital discharge, with blood work revealing absent parasitemia and normalizing anemia and liver function values. To our knowledge, this is the second case of babesiosis reported in a patient treated with an anti–tumor necrosis factor (TNF) agent. The first report involved a patient in Wisconsin with underlying rheumatoid arthritis treated with etanercept (50 mg weekly) and prednisone (5 mg daily) in whom Babesia

Antiretroviral medication for preventing HIV infection in nonoccupational settings

HIV is primarily transmitted through unprotected sexual encounters, contaminated needles and from mother to child during the peripartum period or while breast-feeding. Several evidence-based approaches are used for preventing HIV transmission that can be broadly categorized into pharmacologic and