A double-blind randomized controlled trial of antenatal mebendazole to reduce low birthweight in a hookworm-endemic area of Peru.

OBJECTIVE: To assess the effect on birthweight of antenatal mebendazole plus iron vs. placebo plus iron in a highly hookworm-endemic area. METHODS: Double-blind, randomized controlled trial set in rural and peri-urban communities in the Peruvian Amazon region. A total of 1042 second trimester pregnant women between the ages of 18 and 44 years were recruited from April to November 2003, and followed to July 2004. Women were randomly assigned to receive either mebendazole (500 mg single dose) plus iron supplements (60 mg elemental iron daily) or placebo plus iron supplements. The primary outcome was mean infant birthweight and secondary measures included proportion of low birthweight babies and maternal anaemia. RESULTS: The prevalence of hookworm infection was 47.5%. There were no differences between intervention groups in mean birthweight (3104 g vs. 3090 g, P = 0.629), proportion of low birthweight (<2500 g; 8.1%vs. 8.7%, P = 0.755) or maternal anaemia in the third trimester [33.0% (158/479) vs. 32.3% (152/471), P = 0.815]. However, the proportion of very low birthweight (<1500 g) was significantly lower in the mebendazole group [0% (0/479) vs. 1.5% (7/471), P = 0.007]. CONCLUSIONS: This trial provides additional evidence for the use of anthelmintics, over and above iron supplementation, within antenatal care programmes in hookworm-endemic areas. Benefits of de-worming may be higher in countries not having an antenatal iron supplementation programme or where intensity of hookworm infections is higher.

Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis.

We report the case of a 23-year-old Caribbean man with disseminated strongyloidiasis (co-infected with human T cell lymphotropic virus I/II)), severe hypoalbuminemia, and a paralytic ileus. Subcutaneous ivermectin (200 microg/kg) was administered daily for 14 days because of the inability to effectively administer oral albendazole and oral ivermectin. Three hours after the third daily dose of oral ivermectin, the serum ivermectin concentration was only 0.8 ng/mL, but it increased several fold to 5.8 ng/mL 16 hours after the first dose of subcutaneous ivermectin. During the course of subcutaneous treatment, ivermectin clearance was higher than expected (46.0 L/hour, normal = 31.8 L/hour). This is likely the result of severe hypoalbuminemia since ivermectin is highly protein bound. The ability to achieve adequate levels of ivermectin after oral administration in patients with disseminated strongyloidiasis may be impaired, highlighting the need for alternative routes of administration of ivermectin in these patients.

Ross River virus disease reemergence, Fiji, 2003-2004.

We report 2 clinically characteristic and serologically positive cases of Ross River virus infection in Canadian tourists who visited Fiji in late 2003 and early 2004. This report suggests that Ross River virus is once again circulating in Fiji, where it apparently disappeared after causing an epidemic in 1979 to 1980.

Death related to albendazole-induced pancytopenia: case report and review.

Albendazole is a benzimidazole with wide spectrum coverage as an antiparasitic drug. Reported side effects have been minimal. We report the case of a patient who died with severe prolonged pancytopenia beginning during the third week of therapy for a pulmonary echinococcal cyst. This case was a 68-year-old man who presented with a large cystic lung mass. His medical history was significant for Child-Pugh class B cirrhosis. A prolonged course of albendazole was initiated. Two weeks later, the patient presented in septic shock with severe pancytopenia. The patient was initially resuscitated, but died after 10 days with no marrow recovery. Autopsy was consistent with albendazole-induced pancytopenia. This is the third human case of pancytopenia and the first death reported in relation to albendazole-induced pancytopenia. Neutropenia seems to be related more to higher dosage and longer duration of use. Albendazole sulfoxide peak dose and half life are significantly prolonged by liver disease and concomitant administration of certain drugs. The severity and duration of albendazole-induced pancytopenia in this case was likely related to the underlying liver disease. Frequent serial monitoring of blood counts and cessation of medication with any evidence of marrow toxicity in such patients is warranted.

Malaria "epidemic" in Quebec: diagnosis and response to imported malaria.

BACKGROUND: Imported malaria is an increasing problem. The arrival of 224 African refugees presented the opportunity to investigate the diagnosis and management of imported malaria within the Quebec health care system. METHODS: The refugees were visited at home 3-4 months after arrival in Quebec. For 221, a questionnaire was completed and permission obtained for access to health records; a blood sample for malaria testing was obtained from 210. RESULTS: Most of the 221 refugees (161 [73%]) had had at least 1 episode of malaria while in the refugee camps. Since arrival in Canada, 87 (39%) had had symptoms compatible with malaria for which medical care was sought. Complete or partial records were obtained for 66 of these refugees and for 2 asymptomatic adults whose children were found to have malaria: malaria had been appropriately investigated in 55 (81%); no malaria smear was requested for the other 13. Smears were reported as positive for 20 but confirmed for only 15 of the 55; appropriate therapy was verified for 10 of the 15. Of the 5 patients with a false-positive diagnosis of malaria, at least 3 received unnecessary therapy. Polymerase chain reaction testing of the blood sample obtained at the home visit revealed malaria parasites in 48 of the 210 refugees (23%; 95% confidence interval [CI] 17%- 29%). The rate of parasite detection was more than twice as high among the 19 refugees whose smears were reported as negative but not sent for confirmation (47%; 95% CI 25%- 71%). INTERPRETATION: This study has demonstrated errors of both omission and commission in the response to refugees presenting with possible malaria. Smears were not consistently requested for patients whose presenting complaints were not "typical" of malaria, and a large proportion of smears read locally as "negative" were not sent for confirmation. Further effort is required to ensure optimal malaria diagnosis and care in such high-risk populations.

Malaria epidemics and surveillance systems in Canada.

In the past decade, fluctuations in numbers of imported malaria cases have been seen in Canada. In 1997 to 1998, malaria case numbers more than doubled before returning to normal. This increase was not seen in any other industrialized country. The Canadian federal malaria surveillance system collects insufficient data to interpret these fluctuations. Using local (sentinel), provincial, federal, and international malaria surveillance data, we evaluate and interpret these fluctuations. Several epidemics are described. With an ever-increasing immigrant and refugee population of tropical origin, improved surveillance will be necessary to guide public health prevention policy and practice. The Canadian experience is likely to be generalizable to other industrialized countries where malaria is a reportable disease within a passive surveillance system.

Comparison of blood smear, antigen detection, and nested-PCR methods for screening refugees from regions where malaria is endemic after a malaria outbreak in Quebec, Canada.

The importation of malaria into a region where it is not endemic raises many concerns, including the timely delivery of appropriate care, safety of the blood supply, and the risk of autochthonous transmission. There is presently no consensus on the best way to screen mobile populations for malaria. Between August 2000 and March 2001, 535 refugees arrived in Quebec, Canada, from Tanzanian camps. Within 4 weeks of resettlement of the first group of 224, the McGill University Centre for Tropical Diseases noted an outbreak of malaria across the province (15 cases over a 3-week period). This group (group 1) was traced and screened for malaria between 3 and 4 months after arrival in Canada. Subsequent groups of 106 and 205 refugees were screened immediately upon arrival in Canada (group 2) and immediately prior to their departure from refugee camps (group 3), respectively. A single EDTA-blood sample was obtained from 521 refugees for testing by thick and thin blood smears (groups 1 and 2), antigen detection (ICT Malaria Pf and OptiMAL; group 1 only), and nested PCR (all groups). Overall, 98 of 521 refugees were found to be infected (18.8%). The vast majority of infections (81 of 98) were caused by Plasmodium falciparum alone. Using PCR as the "gold standard," both microscopy (sensitivity, 50%; specificity, 100%) and antigen detection (ICT sensitivity, 37.5%; ICT specificity, 100%; OptiMAL sensitivity, 29.1%; OptiMAL specificity, 95.6%) performed poorly. None of the PCR-positive subjects were symptomatic at the time of testing, and only two had recently had symptoms compatible with malaria (with or without diagnosis and treatment). Active surveillance of migrants from regions of intense malaria transmission can reduce the risk of morbidity in the migrant population and mitigate against transmission to the host population. Our data demonstrate that PCR is, by far, the most powerful tool for such surveillance.

Novel prevention program for trichinellosis in inuit communities.

Repeated outbreaks of trichinellosis caused by the consumption of Trichinella-infected walrus (Odobenus rosmarus) meat, which have sometimes led to serious morbidity, have stimulated Inuit communities in Nunavik (northern Quebec), Canada, to develop an innovative trichinellosis prevention program. The program involves preconsumption testing of meat samples from harvested walrus at a regional laboratory and the rapid dissemination of the results of such testing to communities. Local health authorities in Inukjuak conducted an epidemiological investigation after testing identified Trichinella-positive walrus meat in September 1997. This report describes the events that occurred before, during, and after the trichinellosis outbreak and also documents how the prevention program contributed to successful resolution of the outbreak.