The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

BACKGROUND: The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. METHODS: Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. RESULTS: In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years. CONCLUSION: The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It is proposed to use a threshold incidence of > 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk.

[A fifth plasmodium that can cause malaria]. / En femte plasmodiumart som kan gi malaria.

BACKGROUND: Since 2004, malaria with a "fifth" plasmodium, Plasmodium knowlesi (common in macaque monkeys), has been diagnosed in a number of people in Southeast Asia. This article gives a short overview of the epidemiology, clinical picture, diagnostics and treatment of P. knowlesi infection. MATERIAL AND METHODS: The article is mainly based on articles published in international journals during the last five years. RESULTS: Most cases have been diagnosed in the Malaysian state Sarawak on the island of Borneo. The disease usually presents in the same way as other types of malaria, with the exception that fever spikes comes at 24-hour intervals. Microscopy findings resemble those for P. malariae in the early phase of the disease and many patients have been diagnosed wrongly. Without treatment a serious clinical picture may develop, blood findings may be as serious as for P. falciparum infection and death may occur. Chloroquine tablets are indicated in light infections, while parenteral therapy with artesunate or quinine is necessary in seriously affected patients. P. knowlesi infection has been reported among tourists in Malaysia. INTERPRETATION: The risk of contracting P. knowlesi infection as well as other types of malaria is low in Malaysia and other regions where P knowlesi occurs.

Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response.

UNLABELLED: A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon alpha-2b (1.5 microg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, -0.1 to +13.9). CONCLUSION: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.

Reversibility of schistosomal periportal thickening/fibrosis after praziquantel therapy: a twenty-six month follow-up study in Ethiopia.

To study outcome determinants of schistosomal periportal thickening/fibrosis (PPT/F), 199 subjects (mean age = 24.0 years, range = 7-68 years), 109 with mild (image pattern C) PPT/F, 69 with moderate (image pattern D) PPT/F, and 21 with severe (image patterns E and F) PPT/F were treated with praziquantel and evaluated every six months for a mean duration of 26 months. Subjects excreting Schistosoma mansoni eggs during any of the six-month evaluations were offered repeat treatment. Thirty-five had some improvement, and 69 had total resolution of PPT/F, of which 63.8% resolved within one year. Compared with subjects with moderate lesions, a significantly higher proportion of subjects with mild lesions had resolution/improvement of PPT/F (40.6% versus 69.7%, P < 0.001). Subjects with severe PPT/F showed no improvement. Resolution of PPT/F was significantly more frequent at a younger age, among seronegative for hepatitis B virus and among those with a lower frequency of post-treatment recurrence of S. mansoni infections.

Intensity of Schistosoma mansoni, hepatitis B, age, and sex predict levels of hepatic periportal thickening/fibrosis (PPT/F): a large-scale community-based study in Ethiopia.

To elucidate determinants of morbidity in schistosomiasis mansoni, a community-based study was undertaken involving 2,451 subjects (mean age, 18.8 +/- 15.3 [SD] years) from four endemic sites in Ethiopia. Overall prevalence of infection was 65.9%, reported blood in stools was 35.8%, and schistosomal periportal thickening/fibrosis (PPT/F) was 4.6%. Similarly, 43.2% were positive for at least one marker of hepatitis B virus (HBV), 5.3% were HBsAg positive, and 1.3% were anti-hepatitis C virus (HCV) positive. Prevalence of PPT/F increased significantly with increasing community prevalence and intensity of S. mansoni infection. In a multiple logistic regression analysis, intensity of egg excretion, markers of HBV infection, age, and male sex were significantly associated with PPT/F, whereas co-infection with other intestinal helminths was associated with lower odds for PPT/F. HCV was not associated with S. mansoni infection or with schistosomal PPT/F. In conclusion, integrated helminth control targeting school-aged children, who have the highest burden infection, should be used to substantially reduce the risk of periportal fibrosis.

Reduced serum concentrations of retinol and alpha-tocopherol and high concentrations of hydroperoxides are associated with community levels of S. mansoni infection and schistosomal periportal fibrosis in Ethiopian school children.

To study the relationship between micronutrient malnutrition and schistosomiasis mansoni, a cross-sectional study was undertaken involving 421 schoolchildren (mean age 12.6 years; 333 from schistosomiasis mansoni-endemic villages (Workemado and Sille) and 88 non-endemic controls from Sheno). Prevalence of schistosomiasis mansoni infection in Workemado and Sille was comparable (90.6% versus 95%, respectively), and prevalence of PPF in Workemado was significantly higher than in Sille (7.0% versus 0.6%, P < 0.001). Compared with non-endemic controls, serum retinol concentrations were significantly lower and hydroperoxides were significantly higher in subjects from schistosomiasis mansoni-endemic areas. Furthermore, serum alpha-tocopherol concentrations in subjects from an area with high prevalence of PPF were significantly reduced while the concentrations in subjects from an area with low prevalence of PPF were comparable to the levels found in non-endemic healthy controls. In conclusion, micronutrient malnutrition and oxidative stress are associated with Schistosoma mansoni infection and levels of schistosomal PPF.

The low and declining risk of malaria in travellers to Latin America: is there still an indication for chemoprophylaxis?

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers. Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest API's in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

[Histoplasmosis among travellers to Central America]. / Histoplasmose blant reisende til Mellom-Amerika.

BACKGROUND: In April 2004, the Norwegian Institute of Public Health was notified about an outbreak of a respiratory illness among participants on a cultural-historical theme tour to Central America. One patient was examined in a Swedish hospital where the clinician suspected histoplasmosis, which later was verified by serology and by culture of Histoplasma capsulatum. In order to describe the outbreak and identify the possible source of infection, a clinical and epidemiological study was conducted. MATERIAL AND METHODS: A questionnaire on symptoms, treatment and participation in various activities was sent to all the tour participants. Reminders were sent by e-mail. In addition, some participants underwent a more detailed clinical examination. RESULTS: 19 of the 21 travellers completed the questionnaire. All travellers had visited several caves inhabited by bats in El Salvador and Guatemala. During the last 10 days of the journey, 16 of the respondents (84%) acquired a respiratory illness that lasted for more than 3 weeks. The diagnosis was confirmed by serology in 8 of the 14 tested cases. Antibacterial therapy was given to 11 patients and antifungal therapy to 3 patients. Only one patient was hospitalised. INTERPRETATION: The described outbreak of histoplasmosis was probably caused by exposure to Histoplasma capsulatum during a visit in bat-infested caves. Due to the increasing popularity of adventure and theme travels, this disease may become more frequent in our population. The condition should be considered in travellers with prolonged respiratory illness after visits to caves or other closed environments with little circulation of air that are potentially contaminated with bat or bird droppings. Persons with immunosuppression may develop severe illness, and should consider avoiding places with increased risk.

Repellent efficacy of four commercial DEET lotions against Amblyomma hebraeum (Acari: Ixodidae), the principal vector of Rickettsia africae in southern Africa.

African tick bite fever, caused by Rickettsia africae, is an emerging zoonotic infection in rural sub-Saharan Africa and the French West Indies. We tested the repellent efficacy of four commercial diethyl-3-methylbenzamide (DEET) lotions against Amblyomma hebraeum Koch, the principal vector of R. africae in southern Africa, by using a human bioassay in which repellent-treated fingers were presented to questing tick nymphs hourly for 4h. Three lotions with 19.5, 31.6 and 80% DEET concentrations, respectively, had a repellent efficacy of > or =90% at 1h post-application, of > or =77% at 2h post-application and of <70% during the rest of the experiment. By contrast, a lotion with 2% DEET plus 1% citronella oil provided only a 59% repellency at 1h post-application, with a drop to <22% during the following hours. Hourly negative control trials repelled <5% of tick attacks. Our results suggest that commercial repellents containing > or =19.5% DEET provide a significant but short-lasting protection against questing A. hebraeum ticks.

African tick bite fever in travelers to rural sub-Equatorial Africa.

To estimate the incidence of, identify risk factors for, and describe the clinical presentation of travel-associated African tick bite fever (ATBF), a rapidly emerging disease in travel medicine, we prospectively studied a cohort of 940 travelers to rural sub-Equatorial Africa. Diagnosis was based on suicide polymerase chain reaction and the detection of specific antibodies to Rickettia africae in serum samples by multiple-antigen microimmunofluorescence assay, Western blotting, and cross-adsorption assays. Thirty-eight travelers, 4.0% of the cohort and 26.6% of those reporting flulike symptoms, had ATBF diagnosed. More than 80% of the patients had fever, headache, and/or myalgia, whereas specific clinical features such as inoculation eschars, lymphadenitis, cutaneous rash, and aphthous stomatitis were seen in < or = 50% of patients. Game hunting, travel to southern Africa, and travel during November through April were found to be independent risk factors. Our study suggests that ATBF is not uncommon in travelers to rural sub-Saharan Africa and that many cases have a nonspecific presentation.

African tick bite fever.

African tick bite fever is an acute febrile illness that is frequently accompanied by headache, prominent neck muscle myalgia, inoculation eschars, and regional lymphadenitis. The disease is caused by Rickettsia africae, a recently identified spotted fever group rickettsia, which is transmitted by ungulate ticks of the Amblyomma genus in rural sub-Saharan Africa and the French West Indies. Whereas reports on African tick bite fever in indigenous populations are scarce, the number of reported cases in travellers from Europe and elsewhere has recently increased significantly. Treatment with doxycycline is associated with rapid recovery in most patients. An immunofluorescence assay is recommended for the diagnosis but seroconversion is commonly delayed and this limits the usefulness of the test. Travellers to endemic areas should be informed of the risk of contracting African tick bite fever and be encouraged to take personal protective measures against tick bites.

Proceedings of a joint meeting between the Norwegian Society of Infectious Diseases and the Royal Society of Tropical Medicine and Hygiene, Oslo, 20 June 2008.

This paper presents the proceedings of a scientific meeting that was held between the Royal Society of Tropical Medicine and Hygiene and the Norwegian Infectious Diseases Society at Ullevål University Hospital, Oslo on 20 June 2008. Seven speakers updated the audience on recent advances in relevant issues, including international maternal and child health, podoconiosis, schistosomiasis and HIV, leprosy in the UK, rapid diagnostic tests for malaria, delayed diagnosis of tuberculosis and the Global Filariasis Programme. The meeting ended with a series of case presentations.

Gastro-intestinal symptoms associated with intense Schistosoma mansoni infection affect class-attentiveness of schoolchildren in Ethiopia.

OBJECTIVE: To assess effect of subtle morbidities related to Schistosomiasis mansoni on class-attentiveness of schoolchildren. METHODS: A cross-sectional study was undertaken involving 568 schoolchildren (mean age 13.4 years; 333 from Schistosoma mansoni endemic villages (Sille and Worke-Mado) and 235 from the non-endemic town Sheno. A questionnaire on signs and symptoms of ill-health was administered to all study subjects. In addition, parasitological and nutritional anthropometric data were collected. All study subjects from S. mansoni endemic areas were treated with praziquantel and albendazol while children from the non-endemic town were only treated with albendazol.FindingsPrevalence of S. mansoni infection was 95% in Sille and 90.6% in Worke-Mado. Overall, among schoolchildren from S. mansoni endemic areas, 36.3% were under-nourished; 66.4% reported easy fatigue/listlessness; 61.3% had abdominal cramps with bloody-mucoid stools, and 17.7% reported to have severe and frequent abdominal cramps which distracted their class-attentiveness. The latter two symptoms were significantly associated with intensity of S. mansoni infection. Among schoolchildren from the non-endemic town Sheno, only 8.9% were under-nourished, 20% reported infrequent abdominal cramps and none had symptoms that were severe enough to affect class-attentiveness. CONCLUSION: Symptoms associated with intense S. mansoni infection may negatively affect class-attentiveness of schoolchildren which may have important implications on their overall educational achievements. Further detailed intervention-based prospective studies are recommended to validate these findings which, if confirmed, could further justify school-age targeted praziquantel-based control of schistosomiasis.

Drug resistance of Mycobacterium tuberculosis in the Sunamganj District of Bangladesh.

Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries need to monitor the patterns and trends of anti-TB drug resistance. Such data assess the quality of control programmes and help forecast future trends of drug resistance. It will also help to establish guidelines for TB therapy. The aim of the current study was to describe the rate of drug-resistant Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Bacterial isolates were collected from sputum smear positive (ss+) patients who attended the National TB Programme from November 2003 to December 2004. A total of 95 isolates was tested for susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) at the National Reference Laboratory for Mycobacteria at the Norwegian Institute of Public Health (NIPH), Oslo. The total resistance among new cases to any drug was 31%. For SM it was 18%, INH 23%, RMP 2%, EMB 10% and 2% were multidrug-resistant (MDR). The National Tuberculosis Programme (NTP) in Sunamganj is still effective, although the high resistance to INH is alarming. An increased risk of treatment failure has been demonstrated in areas with high levels of INH resistance, and a high proportion of INH resistant cases may develop resistance to RMP during treatment.

Heterogeneity of Mycobacterium tuberculosis isolates in Sunamganj District, Bangladesh.

A total of 111 Mycobacterium tuberculosis isolates from new pulmonary tuberculosis patients, living in the rural Sunamganj district in northern Bangladesh were characterized with IS6110 restriction fragment length polymorphism analyses and spoligotyping. Only 3 of the isolates belonged to the W-Beijing genotype of M. tuberculosis. A high degree of diversity indicated that the spread of M. tuberculosis, in this rural area, was not caused by closely related genotypes. The tuberculosis cases in the current study were less likely to represent recent transmission than what is commonly observed in urban parts of south-east Asia. It was indicated that the tuberculosis cases of this isolated area, of a high-incidence country, represented those of an established epidemic, not yet influenced by recently disseminated strains.

Increased levels of soluble CD40L in African tick bite fever: possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets.

The pathophysiological hallmark of spotted fever group rickettsioses comprises infection of endothelial cells with subsequent infiltration of inflammatory cells. Based on its ability to promote inflammation and endothelial cell activation, we investigated the role of CD40L in African tick bite fever (ATBF), caused by Rickettsia africae, using different experimental approaches. Several significant findings were revealed. 1) Patients with ATBF (n = 15) had increased serum levels of soluble CD40 ligand (sCD40L), which decreased during follow-up. 2) These enhanced sCD40L levels seem to reflect both direct and indirect (through endothelial cell activation involving CX3CL1-related mechanisms) effects of R. africae on platelets. 3) In combination with sCD40L, R. africae promoted a procoagulant state in endothelial cells by up-regulating tissue factor and down-regulating thrombomodulin expression. 4) Although the R. africae-mediated activation of platelets involved TLR2, the combined procoagulant effects of R. africae and sCD40L on endothelial cells involved TLR4. 5) Doxycycline counteracted the combined procoagulant effects of R. africae and sCD40L on endothelial cells. Our findings suggest an inflammatory interaction between platelets and endothelial cells in ATBF, involving TLR-related mechanisms. This interaction, which includes additive effects between sCD40L and R. africae, may contribute to endothelial inflammation and hypercoagulation in this disorder.

Sub-acute neuropathy in patients with African tick bite fever.

African tick bite fever (ATBF) caused by Rickettsia africae is an emerging health problem in travellers to sub-Saharan Africa. We here present 6 patients with evidence of long-lasting sub-acute neuropathy following ATBF contracted during safari trips to southern Africa. Three patients developed radiating pain, paresthaesia and/or motor weakness of extremities, 2 had hemi-facial pain and paresthaesia, and 1 developed unilateral sensorineural hearing loss. When evaluated 3-26 months after symptom onset, cerebrospinal fluid samples from 5 patients were negative for R. africae PCR and serology, but revealed elevated protein content in 3 and mild pleocytosis in 1 case. Despite extensive investigations, no plausible alternative causes of neuropathy could be identified. Treatment with doxycycline in 2 patients had no clinical effect. Given the current increase of international safari tourism to sub-Saharan Africa, more cases of sub-acute neuropathy following ATBF may well be encountered in Europe and elsewhere in the y to come.