The field strain of Haemonchus contortus has a long history of anthelmintic resistance. To understand this phenomenon, the benzimidazole resistance profile was characterized from the Malaysian field-resistant strain by integrating phenotypic, genotypic and proteomic approaches. The faecal egg count reduction test (FECRT) demonstrated that benzimidazole resistance was at a critical level in the studied strain. The primary resistance mechanism was attributed to F200Y mutation in the isotype 1 β-tubulin gene as revealed by AS-PCR and direct sequencing. Furthermore, the protein response of the resistant strain towards benzimidazole (i.e., albendazole) treatment was investigated via two-dimensional difference gel electrophoresis (2D-DIGE) and tandem liquid chromatography-mass spectrometry (LC-MS/MS). These investigations illustrated an up-regulation of antioxidant (i.e., ATP-binding region and heat-shock protein 90, superoxide dismutase) and metabolic (i.e., glutamate dehydrogenase) enzymes and down-regulation of glutathione S-transferase, malate dehydrogenase, and other structural and cytoskeletal proteins (i.e., actin, troponin T). Findings from this study are pivotal in updating the current knowledge on anthelmintic resistance and providing new insights into the defence mechanisms of resistant nematodes towards drug treatment.
A study to determine the effect of antihelminthic treatment on growth and nutritional status was undertaken on 103 children in the second grade of primary school, 71 of whom were found to be infected with Ascaris lumbricoides or Trichuris trichiura. The median Ascaris and Trichuris intensities in the infected group were 19,600 (range; 0-488,000) and 2,800 (range; 0-84,600) eggs per gram of feces respectively. Forty-three children harbored both types of worm. Fourteen weeks after two 400 mg doses of albendazole were administered to infected children, the increases in weight, height, weight for age, height for age and weight for height were significantly higher among infected children than controls who were uninfected at baseline. The observed gains were independent of sex and socioeconomic status. Decrease in log transformed Trichuris intensity correlated with increases in weight (r=0.24; p=0.02) and weight for age (r=0.20; p=0.06) but decrease in Ascaris intensity did not correlate with increases in any of the anthropometric parameters. The results suggest that antihelminthic treatment has beneficial short-term effects on growth and nutritional status of a modest magnitude among early primary schoolchildren in the area.
Stool examination of 249 early primary schoolchildren at 2 schools in north-eastern peninsular Malaysia revealed that 73 were infected with Ascaris lumbricoides, 103 with Trichuris trichiura, and 18 with hookworms. Infected children were treated with a single dose of 400 mg of albendazole. The school attendance records during a 60 d period before treatment and 2 consecutive 60 d periods after treatment were examined. The absenteeism rate did not improve more among infected children after treatment than it did among the uninfected control children. The correlation between worm intensity and the number of lost school-days was poor. There was no evidence that intestinal helminthiasis caused school absenteeism among this group of children.
Intestinal permeability of 246 early primary schoolchildren at 2 schools (106 of whom were infected with intestinal helminths) was assessed by using the lactulose/mannitol differential absorption test. The ratio of the urinary recoveries of lactulose and mannitol was determined after oral administration of a standard solution of the 2 sugars. Assessment of intestinal permeability was repeated on 100 infected children after treatment and on a cohort of 68 uninfected children. Infected and uninfected groups were compared with respect to baseline lactulose/mannitol ratio (L/M1) and change in lactulose/mannitol ratio between assessments (delta L/M). The correlations between baseline intensity of infection and L/M1, and between fall in intensity and delta L/M, were evaluated. Based on a crude index of socioeconomic status, each child was assigned to one of 3 socioeconomic groups; all but 3 children belonged to either groups 2 or 3. Trichuris trichiura and Ascaris lumbricoides were the 2 predominant infections; the hookworm infection rate was relatively low. The results suggested that helminthiasis exerted only a marginal effect on intestinal permeability, the impact of which in children from lower socioeconomic backgrounds was negligible in comparison with the cumulative effects of other factors.
A previous study had suggested that local strains of goat trichostrongyles, comprising largely Haemonchus contortus, might have developed resistance to benzimidazole anthelmintics. A trial involving 18 goats was conducted to confirm this. There was a significant (P < 0.01) reduction in worm burdens in goats given levamisole, but this was not so for those animals given albendazole, fenbendazole, oxfendazole and mebendazole (P > 0.05).
A community study was carried out to evaluate the efficacy of a 3-day course of 400 mg albendazole daily in the treatment of Trichuris trichiura and Giardia intestinalis infection. This treatment regimen was effective in the treatment of Trichuris trichiura and Giardia intestinalis infection with cure rates of 91.5% and 96.6% respectively. Uses of a 3-day course of 400 mg albendazole daily should be considered in mass or targeted soil-transmitted helminths chemotherapy particularly in areas where the prevalence of Trichuris trichiura is high and polyparasitism is common.
The efficacy of a single-dose 400 mg albendazole to treat Ascaris, Trichuris and hookworm infection was studied in Orang Asli community. Kato-Katz examination was performed on fecal samples which were collected before treatment, 1 and 4 months after treatment. A total of 123 children were involved in all three surveys. The cure rate of Ascaris infection was 97.4% and the egg reduction after treatment was 99.9%. The cure rate for hookworm infection was 93.1% with 96.6% egg reduction. Although the cure rate was low in Trichuris infection (5.5%), egg reduction was more evident (49.1%). The reinfection rate at 4 months after treatment was 54.5%, 3.6% and 10.3% for Ascaris, Trichuris and hookworm infection, respectively. Within 4 months after treatment almost one-fifth children with Ascaris and hookworm infection reached pre-treatment intensity infection. In Trichuris infection, however more than half of the children reached their pre-treatment intensity infection at 4 months after treatment. Findings suggest that 4-monthly targeted periodic treatment with 400 mg single-dose albendazole in highly endemic areas can have a significant impact on intensity infection of Ascaris and hookworm, but not on Trichuris infection.
Fecal specimens collected from 456 school children in Gombak, Malaysia, revealed an overall prevalence rate of 62.9%. The most common parasite found was Trichuris trichiura (47.1%) followed by Giardia intestinalis (14.7%), Entamoeba coli (11.4%), Entamoeba histolytica (9.9%) and Ascaris lumbricoides (7.9%). Infection rates were high among the Indonesian immigrant workers' children (90%) followed by the Orang Asli (79.5%), Malay (59.4%) and Indians (36.4%). Females (66.3%) had a higher prevalence rate than the males (58.5%). The prevalence of infection was found to be associated with the socio-economic status, water supply, sanitary disposal of feces and family size. Albendazole administered as a single dose (400 mg) was found to be effective against Ascaris (100%) and hookworm (92.3%) but was not effective against Trichuris (39.2%).
This study examines the persistence of predisposition to Ascaris lumbricoides and Trichuris trichiura during repeated chemotherapy in an urban community in Kuala Lumpur, Malaysia. Significant predisposition was observed over 2 periods of reinfection with and without age-standardization of data. Analysis of different age groups indicated that predisposition was most strongly detectable in the younger age classes. The intensities of infection with both parasites were strongly correlated at each cycle of intervention, suggesting that individuals were similarly predisposed to both species.
Neurocysticercosis, infection of the central nervous system (CNS) by larvae of the pork tapeworm Taenia solium, is the commonest neuroparasitic infection in humans. However in countries as in Malaysia it poses a diagnostic problem as the disease in not seen amongst the local population; however with the arrival of immigrant workers, a number of cases have recently been diagnosed. There were 3 cases of neurocysticercosis reported in our centre over the last 5 years.
Five local Malaysian patients with clinical manifestations consistent with lymphatic filariasis were referred to our medical centre between 2003 and 2006. Although no microfilariae (mf) were detected in their nocturnal blood samples, all were diagnosed to have lymphatic filariasis on the basis of clinical findings and positive serology results. PCR on their blood samples revealed that two of the patients were infected with Brugia pahangi, an animal filarial worm hitherto not known to cause human disease in the natural environment. All the patients were successfully treated with anti-filarial drugs: four patients were treated with a combination of diethylcarbamazine (DEC) and albendazole, and one with doxycycline. Four of them were residents of Petaling Jaya, a residential suburbia located 10 km southwest of Kuala Lumpur city, Malaysia. The fifth patient was a frequent visitor of the suburbia. This suburbia has no history or record of B. malayi infection. The most likely vector of the worm was Armigeres subalbatus as extensive entomological surveys within the suburbia revealed only adult females of this mosquito species were infected with B. pahangi larvae. Wild monkeys caught in the suburbia were free from B. pahangi mf, but domestic cats were mf positive. This suggests that infected cats might be the source of the zoonotic infection in the suburbia.
This study was carried out to develop a health education learning package (HELP) about soil-transmitted helminth (STH) infections, and to evaluate what impact such a package could have in terms of reducing the incidence and intensity of STH infections among Orang Asli schoolchildren in Pahang, Malaysia.
Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).
Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.
BACKGROUND: Hookworm infection is one of the important Neglected Tropical Diseases (NTD) in the world. It was previously more prevalent in the northern and southern parts of Iran with a prevalence rate higher than 40% in some endemic regions; nevertheless, the infection rate has decreased to less than 1%. This study aimed to determine prevalence and molecular aspects of hookworm infections in rural inhabitants of Fouman County, Guilan Province, northern Iran.
METHODS: This cross-sectional study was performed in 31 villages of Fouman district in Guilan Province, northern Iran during 2015-2016. Stool samples were collected from 1500 rural inhabitants and examined by formalin ethyl-acetate concentration as well as agar plate culture techniques. After treatment with albendazole, adult hookworms were isolated. Following DNA extraction, PCR amplification of ITS2-rDNA region was performed and the product was sequenced, followed by genetic variation analysis.
RESULTS: Of 1500 samples, one case was morphologically diagnosed as N. americanus. In addition, molecular characterization verified the presence of N. americanus, showing more than 95% similarity with sequences of N. americanus present in GenBank. The patient showed no clinical symptoms and a mild hypereosinophilia was the only laboratory finding observed.
CONCLUSION: A reduced prevalence of human hookworms was demonstrated within Guilan Province located in north of Iran. The N. americanus originated from Guilan had a high homology with the isolates found in Japan, Laos, Malaysia, and Australia.
Introduction: Ascariasis is a parasitic infection, which commonly affects immunocompromised patients. Most pa-tients remained asymptomatic during the early larval migration stage and respond well with conventional anti-hel-minthic drugs. Previous literature had reported symptomatic Ascaris infection mimicking bacterial pneumonia and the typical eosinophilia found in Loeffler syndrome was absent in patients on corticosteroids. Thus, a high index of suspicion for ascariasis is needed for immunosuppressed patients presented with infection. We present here a case of severe ascariasis infection in a systemic lupus erythematosus patient. Case description: A 16-year-old boy presented with fever, generalized maculopapular rash associated with neutropenia and thrombocytopenia. He was treated initially as Dengue Fever initially. However his symptoms did not resolve at even day 14 of admission. On further assessment, we were convinced he has SLE based upon presence of malar rash, oral ulcers, urinary protein-uria, persistent leucopenia, thrombocytopenia with low complements and ANA positive. He was promptly started on IV hydrocortisone. He showed a good progress in the first few days. On day 5 of admission, he coughed out a round worm which later identified as Ascarisis lumbricoides. He was started on Albendazole. Unfortunately he developed hemoptysis and respiratory compromisation where he required intubation. Post intubation he went into cardiac arrest, which required CPR. Following that event, his condition further deteriorated with multi organ failure. He succumbed to his illness three days later. Conclusion: Immunocompromised patients are prone to opportunistic infections including parasitic infections. we present here a case of ascariasis in an SLE patient who unfortunately succumbed to the illness. Due to the variable clinical symptoms that mimic other infections, screening for parasitic infections needs to be considered especially if the patients do not respond to antibiotics and routine treatments.
Introduction: Strongyloidiasis is endemic in the tropical and subtropical regions. Clinical manifestations of the dis-ease can range from asymptomatic eosinophilia in an immunocompetent host to a wide range of presentations in immunocompromised patients. Failure to consider the diagnosis of strongyloides infection, especially Strongyloides hyperinfection syndrome, is a major contributor of high mortality rate in such cases. Case Description: We report a case of 60 years old gentleman who was admitted to Sarawak General Hospital for a left subtrochanteric femur pathological fracture and the diagnosis of multiple myeloma was made in the same setting. He was started on treat-ment for multiple myeloma which includes high dose steroids. During his course of admission, he was diagnosed with hospital-acquired pneumonia was subsequently initiated with broad-spectrum antibiotics. Despite being exten-sively treated with multiple courses of broad-spectrum antibiotics, he deteriorated clinically, with eventual respirato-ry failure requiring ventilator support and ICU admission. A diagnosis of strongyloides hyperinfection syndrome was made after an incidental discovery of larvae in his sputum, which was later confirmed with stool sample. He was given a one-week course of albendazole 400mg twice daily and clinical improvement was observed. A repeated stool sample also demonstrated clearance of the parasites. Conclusion: This case highlights the need for clinical sus-picion of strongyloides hyperinfection syndrome in cases of unresolved pneumonia, especially for patients with risk factors of underlying immune-deficiency state. Preventive steps such early detection and eradication of strongyloides infection should be undertaken prior to initiation of immuno-suppressive therapy.