Egg Reduction Rate Research Articles

The Appropriate Indicator Should be Used to Assess Treatment Failure in STH Infections

Dear Sir: We write to comment on the article by Humphries and others1 recently published in the American Journal of Tropical Medicine and Hygiene: in our opinion, the study is well conducted, however, we respectfully disagree with the conclusions and in particular with the claim made by the authors about the failure of albendazole treatment of hookworms. We summarize here the reasons of our disagreement: Humphries and others base the claim for albendazole failure in treating hookworm infection on the analysis of cure rate (CR) results that they measured at 61%; however, in the case of infections caused by hookworm and other soil-transmitted helminths (STHs), the CR is not a good indicator of drug efficacy because it is influenced by the intensity of infection at baseline and by the sensitivity of the parasitological method used to recover eggs from stool.2 As a result, it is very difficult to compare CRs obtained in different settings and reach meaningful conclusions about differences in drug efficacy. Our opinion is that drug efficacy in STH infections should be assessed with a more apt indicator, namely the egg reduction rate (ERR). The data presented by Humphries and others show an ERR of over 80% and this corresponds to the normal range of efficacy of albendazole against this parasite,3 as correctly reported by the authors. We would also like to stress the fact that the main objective of preventive chemotherapy against hookworm and other STH infections (those by Ascaris lumbricoides and Trichuris trichiura) is not to achieve cure of infected individuals, but rather to significantly reduce the number of worms harbored by such individuals4; this is because the average observed reduction (that can be measured by counting the number of eggs passed out in feces) is sufficient to cause the parallel decrease: • of transmission (because of the reduced number of eggs contaminating the environment)5; and • of morbidity (because the few surviving worms—that cannot replicate in the human host—cause less harm to the human host).6 As an additional comment, we would also like to express our concern about the method used by the authors to assess drug quality (i.e., in vitro anthelminthic activity), because this method has never been validated for albendazole that is insoluble in water; in addition, in our experience, the key factors in determining the quality of drugs used against STH are the tablet dissolution and disintegration times, and none of them was tested by the authors. Finally, we strongly disagree with the authors' statement that “mebendazole and pyrantel are not any longer recommended for the treatment of hookworm infection”; again, the studies on which the authors formulate their conclusion are based on the evaluation of the cure rate,7,8 and therefore, for the reasons mentioned previously, not conclusive. As a matter of fact, the World Health Organization (WHO) continues to include mebendazole and pyrantel in the list of recommended drugs for the treatment of STH infections. The WHO is seriously concerned about unjustified claims of drug resistance made on the basis of incorrect interpretations of parasitological results and on the poor understanding of the STH biology and control strategies. These claims create uncertainty among the managers of control programs about the efficacy of the control measures to be implemented and undermine the scaling up of STH control activities. As a consequence, a working group reporting to the WHO Strategic and Technical Advisory Group on Neglected Tropical Diseases (NTD) was established with the aim of developing a Standard Operating Procedure to be implemented whenever a control manager suspects a reduction of the drug activity (report available at http://www.who.int/neglected_diseases/NTD_STAG_Report_2011.pdf). Although we hope that this much needed tool will be available before the end of the year, we take this opportunity to invite AJTMH and other scientific journals to carefully assess the grounds on which claims of drug failure are based should similar papers be submitted for publication.

Efficacy of single and double doses of albendazole and mebendazole alone and in combination in the treatment of Trichuris trichiura in school-age children in Uganda

A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400 mg albendazole (ALB) and 500 mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment of Trichuris trichiura. Infected pupils ( n = 611) were randomised to six treatment groups. Three groups received either a single dose of ALB, MBZ or the combination (ALB+MBZ). The other three groups received either a double dose of ALB (ALB/ALB), MBZ (MBZ/MBZ) or the combination (ALB+MBZ/ALB+MBZ). All double doses were given 8 h apart. Children were followed-up weekly for 1 month. Cure rates were significantly higher using double doses compared with single doses (irrespective of drug; z = −4.02, P < 0.0005) as well as using the drug combination compared with single drugs (irrespective of doses; z = −7.64, P < 0.0005). Cure rates measured at Day 7 were significantly higher than on Days 14 and 21 after treatment (Day 14, z = 9.90, P < 0.0005; Day 21, z = 7.36, P < 0.0005). Geometric mean (GM) intensities of positives were significantly lower on Day 7 compared with all other subsequent days ( P < 0.00005), and on Day 28 GM intensities reached pre-treatment levels ( P = 0.096). Whilst there was no difference in egg excretion between single and double doses of the same drug or drug combination ( F (df 1) = 0.28, P = 0.60), the combination treatment resulted in lower egg excretion than use of single drugs ( F (df 2) = 50.90, P < 0.00005). All the tested regimens of ALB and MBZ had low cure rates against T. trichiura in Uganda, but both combination treatments showed satisfactory egg reduction rates 3 weeks after treatment. [ClinicalTrials.gov identifier: NCT01050452]

Schistosoma haematobium Treatment in 1–5 Year Old Children: Safety and Efficacy of the Antihelminthic Drug Praziquantel

BackgroundMorbidity due to schistosomiasis is currently controlled by treatment of schistosome infected people with the antihelminthic drug praziquantel (PZQ). Children aged up to 5 years are currently excluded from schistosome control programmes largely due to the lack of PZQ safety data in this age group. This study investigated the safety and efficacy of PZQ treatment in such children.MethodsZimbabwean children aged 1–5 years (n = 104) were treated with PZQ tablets and side effects were assessed by questionnaire administered to their caregivers within 24 hours of taking PZQ. Treatment efficacy was determined 6 weeks after PZQ administration through schistosome egg counts in urine. The change in infection levels in the children 1–5 years old (n = 100) was compared to that in 6–10 year old children (n = 435).Principal FindingsPre-treatment S. haematobium infection intensity in 1–5 year olds was 14.6 eggs/10 ml urine and prevalence was 21%. Of the 104 children, 3.8% reported side effects within 24 hours of taking PZQ treatment. These were stomach ache, loss of appetite, lethargy and inflammation of the face and body. PZQ treatment significantly reduced schistosome infection levels in 1–5 year olds with an egg reduction rate (ERR) of 99% and cure rate (CR) of 92%. This was comparable to the efficacy of praziquantel in 6–10 year olds where ERR was 96% and CR was 67%.Interpretation/SignificancePZQ treatment is as safe and efficacious in children aged 1–5 years as it is in older children aged 6–10 years in whom PZQ is the drug of choice for control of schistosome infections.

Epidemiology of Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure

A cross-sectional pilot study of hookworm infection was carried out among 292 subjects from 62 households in Kintampo North, Ghana. The overall prevalence of hookworm infection was 45%, peaking in those 11-20 years old (58.5%). In children, risk factors for hookworm infection included coinfection with malaria and increased serum immunoglobulin G reactivity to hookworm secretory antigens. Risk factors for infection in adults included poor nutritional status, not using a latrine, not wearing shoes, and occupation (farming). Although albendazole therapy was associated with an overall egg reduction rate of 82%, 37 subjects (39%) remained infected. Among those who failed therapy, treatment was not associated with a significant reduction in egg excretion, and nearly one-third had higher counts on repeat examination. These data confirm a high prevalence of low-intensity hookworm infection in central Ghana and its association with poor nutritional status. The high rate of albendazole failure raises concern about emerging resistance.

A Standardised Protocol for Evaluation of Anthelminthic Efficacy

A Standardised Protocol for Evaluation of Anthelminthic Efficacy

Efficacy and safety of mefloquine, artesunate, mefloquine–artesunate, tribendimidine, and praziquantel in patients with Opisthorchis viverrini: a randomised, exploratory, open-label, phase 2 trial

Praziquantel is the only drug available for treatment of Opisthorchis viverrini, although in-vivo studies point to activity of mefloquine, artesunate, and tribendimidine against this liver fluke. We aimed to assess the efficacy and safety of these drugs compared with that of praziquantel in patients with O viverrini infection. We did a randomised open-label trial between February and April, 2010, in the Saysetha district, Attapeu Province, Laos. Eligible patients were school children aged 10-15 years who had O viverrini infections. Patients were randomly assigned to one of five different treatment groups by use of a computer-generated randomisation code. We assessed efficacy as cure rate and egg reduction rate in intention-to-treat and per-protocol analyses. The trial was registered with Current Controlled Trials, ISRCTN23425032. 125 children were randomly assigned: 25 received mefloquine, 24 artesunate, 24 mefloquine-artesunate, 27 tribendimidine, and 25 praziquantel. 19 patients were lost to follow-up. In the intention to treat analysis, 14 patients receiving praziquantel were cured compared with none with mefloquine, one with artesunate (odds ratio 0·03, 95% CI 0·004-0·29), one with mefloquine-artesunate (0·03, 0·004-0·29), and 19 with tribendimidine (1·87, 0·60-5·85). Egg reduction rate was 98·4% for praziquantel, 30·2% for mefloquine (egg reduction-rate ratio 1·61, 95% CI 0·21-0·72), 31·5% for artesunate (0·43, 0·23-0·80), 41·3% for mefloquine-artesunate (0·60, 0·31-1·10), and 99·3% for tribendimidine (1·00, 0·44-2·30). Most adverse events were mild or moderate and affected all treatment groups; serious adverse events--vertigo, nausea, vomiting, and anxiety--were reported only by patients taking mefloquine or mefloquine-artesunate. Tribendimidine seems to be at least as efficacious as the drug of choice, praziquantel, for the treatment of O viverrini infections; both drugs were well tolerated. Mefloquine, artesunate, and mefloquine-artesunate did not show an effect. Tribendimidine should be further investigated with large clinical trials. Swiss National Science Foundation, University of Basel.

Efficacy of two praziquantel treatments among primary school children in an area of highSchistosoma mansoniendemicity, Nile Delta, Egypt

Praziquantel is the cornerstone of schistosomiasis control. A number of reports from endemic areas suggest that resistance or tolerance to praziquantel might exist in Schistosoma mansoni. Several explanations were postulated. The present work was designed to test the hypothesis that a low praziquantel (pzq) cure rate in Egypt is due to survival and maturation of immature stages that escaped pzq, which is effective against mature S. mansoni worms only. The study sample included 1351 children attending El Rouse primary school located in El Rouse village, Nile Delta, Egypt. All children received 2 pzq doses (40 mg/kg) 4 weeks apart. Diagnosis of S. mansoni infection and cure assessment were based on examination of 2 Kato slides prepared from a single stool sample collected before and 4 weeks after the first and second treatments. The cure rate was 78·8% after the first treatment and increased significantly to 90·8% after the second treatment. Egg reduction rates were 71·2% and 77·2% after 1 and 2 treatments respectively. Pre-treatment intensity of infection has a great influence on cure and egg reduction rates. Our results confirmed that low praziquantel cure rate, in Egypt, might be attributed, even partially, to survival and maturation of the immature S. mansoni stages that escaped pzq that is effective against mature worms only.

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin againstTrichuris trichiura: A Randomized Controlled Trial

Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 μg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. isrctn.org Identifier: ISRCTN08336605.

Soil transmitted helminth infections and schistosomiasis in school age children in sub-Saharan Africa: Efficacy of chemotherapeutic intervention since World Health Assembly Resolution 2001

Soil transmitted helminth infections (STH) and schistosomiasis constitute major public health challenges among school-age children in sub-Saharan Africa. This review assessed the efficacy of chemotherapeutic intervention in line with the World Health Assembly (WHA) resolution since the passage in 2001. Using the Medline Entrez-Pubmed search, relevant publications were identified via combinations of key words such as helminth infection, school children, chemotherapy, Africa. Albendazole, mebendazole, and praziquantel were the antihelminthic drugs most commonly evaluated. Cure rates >80% and egg reduction rates >90% were recorded in most cases of schistosomiasis using praziquantel. Albendazole was very effective against A. lumbricoides and hookworm infections with majority of the studies recording cure rates >75%, but the efficacy of the drug was poor against T. trichiura. To ensure the realization of the WHA resolution, there is need for regular treatment of school children, development of alternative antihelminthic drugs and vaccines, environmental control measures and health education.

Efficacy and Safety of Mefloquine, Artesunate, Mefloquine‐Artesunate, and Praziquantel againstSchistosoma haematobium: Randomized, Exploratory Open‐Label Trial

Morbidity control of schistosomiasis relies on a single drug, praziquantel. The antimalarial drug mefloquine possesses interesting antischistosomal properties, yet no clinical studies have been performed. We conducted a randomized, exploratory open-label trial to assess the efficacy and safety of mefloquine (25 mg/kg), artesunate (3 doses of 4 mg/kg), mefloquine-artesunate (3 doses of 100 mg artesunate plus 250 mg mefloquine), and praziquantel (40 mg/kg) against Schistosoma haematobium. The effects on Schistosoma mansoni, malaria parasitemia, soil-transmitted helminths, and intestinal protozoa were also determined. A total of 83 S. haematobium-infected schoolchildren were included in the study. Cure rates of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against S. haematobium at day 26 after treatment were 21%, 25%, 61%, and 88%, respectively. Both mefloquine-artesunate and praziquantel resulted in egg reduction rates >95%. Significantly lower egg reduction rates were seen in the artesunate (85%) and mefloquine groups (74%). In children coinfected with S. mansoni, praziquantel and mefloquine-artesunate, but not mefloquine and artesunate alone, resulted in high cure rates and egg reduction rates. Mefloquine, artesunate, and mefloquine-artesunate completely cured infections due to Plasmodium falciparum. No effects were found against soil-transmitted helminths and intestinal protozoa. Abdominal pain was the most frequent adverse event, with a higher incidence among children treated with mefloquine (89%), mefloquine-artesunate (83%), and artesunate (60%) than among children treated with praziquantel (46%). The high efficacy of mefloquine-artesunate against S. haematobium warrants further investigation. Individuals coinfected with Plasmodium and Schistosoma who were treated with a mefloquine-artesunate combination against malaria might have a dual benefit: clearance of malaria parasitemia and reduction of schistosomiasis-related morbidity. Current Controlled Trials identifier: ISRCTN06498763.

English

This study assessed the actual prevalence of geohelminths and the impact of albendazole on parasitic indices in Kotto Barombi and Marumba II. Stools samples were collected from 420 school children and examined using the Kato-katz faecal technique. Participants were treated with 600 mg of albendazole. Baseline prevalence of infections and mean parasite loads were 26.4% and 6226.9e/g (Ascaris lumbricoides), 31.0% and 252.4 e/g (Trichuris trichiura), and 1.4% and 468.0e/g (Necator americanus). Four children (0.9%) were infected with Strongyloides stercoralis. A significant difference of prevalence was observed between the two villages for A. lumbricoides (P = 0.0001) andT. trichiura (P = 0.0005), and parasite loads for T. trichiura (P = 0.0001). Single infection (T. trichiura or A. lumbricoides) and double infection (A. lumbricoides - T. trichiura) were more prevalent. Post treatment control showed a decrease of prevalence and mean parasite load to 24.4% and 2969.5e/g (A. lumbricoides), and 24.0% and 112.8e/g (T. trichiura), and 0.0% for N. americanus and S. stercoralis. Efficacy and egg reduction rates were 84.6% and 55.3% (T. trichiura), 82.0% and 52.2% (A. lumbricoides), and 100.0% for N. americanus and S. stercoralis. These results suggest that geohelminths infections remain a serious health problem in school children in Kotto Barombi focus. Key words: School children, geohelminth, prevalence, parasite load, albendazole, drug efficacy, Kotto Barombi, Marumba II, Cameroon

Effect of Control Strategies on Prevalence, Incidence and Re-infection of Clonorchiasis in Endemic Areas of China

BackgroundA pilot clonorchiasis control project was implemented to evaluate the efficacies of various chemotherapy strategies on prevalence, incidence and re-infection in Heilongjiang Province, China.Methods and FindingsSeven intervention groups (14,139 residents, about 2000 in each group) in heavily or moderately endemic areas were subjected to repeated praziquantel administration from 2001 to 2004. In the selective chemotherapy groups, residents were examined for fecal eggs, and those who tested positive were treated with three doses of 25 mg/kg praziquantel at 5-hour-intervals in one day. However, all residents were treated in the mass chemotherapy groups. In heavily endemic areas, two mass treatments of all residents in 2001 and 2003 reduced the prevalence from 69.5% to 18.8%, while four annual mass treatments reduced the prevalence from 48.0% in 2001 to 8.4% in 2004. Selective annual treatments for egg-positive subjects reduced the egg-positive rates from 54.9% in 2001 to 15.0% in 2004 or from 73.2% in 2001 to 12.3% in 2004. Selective treatments every 6 months significantly reduced the prevalence from 59.5% in 2001 to 7.5% in 2004. All of the repeated treatments reduced EPG (eggs per gram of feces) significantly. The annual mass treatment and selective treatment every 6 months produced lower prevalence and re-infection rates and higher egg reduction rate than annual selective treatments did. In the moderate endemic areas, egg positive rates were 24.8% and 29.7% in 2001 but were 1.9% and 1.3% after 2 or 3 selective treatments. The prevalence, incidence, re-infection rates in a moderately endemic area were significantly lower than those of heavy endemic areas.ConclusionsRepeated mass treatment or selective treatment with praziquantel every 6 to 12 months is highly effective for clonorchiasis control in heavily endemic areas. In contrast, one or two selective treatments with health education is effective in moderately endemic areas.

Efficacy of Artesunate + Sulfamethoxypyrazine/Pyrimethamine versus Praziquantel in the Treatment of Schistosoma haematobium in Children

BackgroundThis study was conducted to determine the efficacy of the antimalarial artemisinin-based combination therapy (ACT) artesunate +sulfamethoxypyrazine/pyrimethamine (As+SMP), administered in doses used for malaria, to treat Schistosoma haematobium in school aged children.Methodology/Principal FindingsThe study was conducted in Djalakorodji, a peri-urban area of Bamako, Mali, using a double blind setup in which As+SMP was compared with praziquantel (PZQ). Urine samples were examined for Schistosoma haematobium on days −1, 0, 28 and 29. Detection of haematuria, and haematological and biochemical exams were conducted on day 0 and day 28. Clinical exams were performed on days 0, 1, 2, and 28. A total of 800 children were included in the trial. The cure rate obtained without viability testing was 43.9% in the As+SMP group versus 53% in the PZQ group (Chi2 = 6.44, p = 0.011). Egg reduction rates were 95.6% with PZQ in comparison with 92.8% with As+SMP, p = 0.096. The proportion of participants who experienced adverse events related to the medication was 0.5% (2/400) in As+SMP treated children compared to 2.3% (9/399) in the PZQ group (p = 0.033). Abdominal pain and vomiting were the most frequent adverse events in both treatment arms. All adverse events were categorized as mild.Conclusions/SignificanceThe study demonstrates that PZQ was more effective than As+SMP for treating Schistosoma haematobium. However, the safety and tolerability profile of As+SMP was similar to that seen with PZQ. Our findings suggest that further investigations seem justifiable to determine the dose/efficacy/safety pattern of As+SMP in the treatment of Schistosoma infections.Trial RegistrationClinicalTrials.gov NCT00510159

IL-18 enhances protective effect in mice immunized with a Schistosoma japonicum FABP DNA vaccine

Two recombinant plasmids, pVAX/SjFABP and pVAX/mIL-18 containing Schistosoma japonicum 14 kDa fatty acid binding protein (SjFABP) and murine IL-18, were constructed and evaluated for their ability to induce immune responses and to protect against S. japonicum challenge in mice. Mice were intramuscularly immunized twice at three-weekly intervals, and challenged with S. japonicum cercariae at 4 weeks after the last vaccination. All animals vaccinated with pVAX/SjFABP alone or plus pVAX/mIL-18 developed specific anti-SWAP ELISA antibody and T lymphocyte proliferation. Co-injection of pVAX/mIL-18 significantly increased the production of IFN-γ and IL-2 compared with pVAX/SjFABP alone, indicating that IL-18 enhances the Th1-dominant immune response. The challenge experiment showed that co-injection of plasmid encoding IL-18 significantly enhances protective effect against S. japonicum infection, as demonstrated by worm reduction rates and the hepatic egg reduction rates 45 days post-challenge. These results indicated that IL-18 may become a novel vaccine adjuvant for development of vaccines against schistosomiasis.

Albendazole and mebendazole have low efficacy against Trichuristrichiura in school-age children in Kabale District, Uganda

Three groups of Trichuris trichiura-infected school-age children were treated with one dose 400mg albendazole, 100mg mebendazole twice daily for 3 d, or 100mg mebendazole twice daily for 5 d. The albendazole study investigated cure and egg reduction rates and found that only 5 of 66 infected children were egg-negative 7 d post-treatment, giving a cure rate of 8% and a geometric mean egg reduction rate of 89%. However, at day 14 post-treatment, all children were again egg-positive with significantly higher egg counts than at day 7 (P<0.001). The two mebendazole studies aimed for the recovery of adult T. trichiura worms. After the 3 d course of mebendazole treatment, only four worms were recovered on days 3-5 after start of treatment from 2 of 34 infected children. With the 5 d course of mebendazole treatment, 10 of 21 infected children expelled a total of 27 worms. In the last case the first worm appeared on day 4 post-treatment, and the highest number of worms was recovered when the study ended at day 7. In conclusion, even with the longest treatment regimen and collecting stool samples over seven consecutive days, only very few worms were recovered. The results of this study suggest that alternative drugs and/or alternative regimens in current control programmes against T. trichiura need renewed attention.

Expression profile, localization of an 8-kDa calcium-binding protein from Schistosoma japonicum (SjCa8), and vaccine potential of recombinant SjCa8 (rSjCa8) against infections in mice

Researches on genes expressed in a cercarial stage-specific manner may help us understand the molecular events and functions during schistosome invasion of skin. A genomic clone encoding 8-kDa calcium-binding protein (SjCa8) specifically expressed in cercariae and skin-stage schistosomulum (transformed within 3 h) was obtained from cercariae. Recombinant protein was expressed in vector pET32a (+) and purified using a Ni-NTA purification system. The target protein SjCa8 was determined by matrix-assisted laser desorption/ionization time-of-flight (TOF)/TOF mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blot revealed SjCa8 can be detected in cercaria and skin-stage schistosomulum but not lung-stage schistosomulum, adult, or egg and was localized to head gland, penetration gland tubes, and penetration glands where Ca(2+) was abundant, and the cercarial tegument (but not tegument of tail) and body-tail junction. Furthermore, SjCa8 was interestingly detected in cercarial secretions. The characterization of SjCa8 indicated that it may undergo structural and physiological modifications, including repair of the surface membrane, changes in permeability that account for the loss of water tolerance, activities of calcium-depending enzymes, and immune signaling, etc. Furthermore, vaccination with rSjCa8 plus adjuvant induced protective effect with 50.39% worm reduction rate and significantly high hepatic and intestine egg reduction rates (54.16%, 50.63%, respectively), which is possibly mediated through an apparent induction of Th1-type immune response for strikingly high level of IgG2a and IgG2b developed in immunized C57BL/6 mice.

Efficacy and side effects of praziquantel treatment against Schistosoma haematobium infection among primary school children in Zimbabwe

We examined the efficacy of praziquantel against Schistosoma haematobium among primary school children during a school-based deworming programme in the Burma Valley commercial farming area and the Nyamaropa rural areas in Zimbabwe, where the disease is highly endemic. Among 767 individuals infected with S. haematobium, 675 (88.0%) received treatment. Two single oral doses of 40mg/kg praziquantel were given 6 weeks apart. Of the 675 participants, heavy infection intensity was more common in males than females (chi(2)=6.61, P=0.010). Six weeks later, 624 participants (92.4%) were successfully followed up. The overall cure rate was 88.5% and the egg reduction rate was 98.2%. The highest cure rate was among those individuals with light infection. Seventy-two individuals remained infected at 6 weeks post treatment, among which 3 and 69 individuals had heavy and light infection, respectively. Forty-six of these children resolved following a second round of treatment at 6 weeks follow-up. Of the remaining children successfully followed-up, 22 resolved after a third round of treatment 6 months later. A wide range of observed mild and transient side effects were not associated with egg intensity. The parasitological cure rate was not associated with gender or age. Our study demonstrates that praziquantel is efficacious against S. haematobium in Zimbabwe, although low levels of persistent infection warrant further investigation.

Efficacy of Current Drugs Against Soil-Transmitted Helminth Infections

More than a quarter of the human population is likely infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) in highly endemic areas. Preventive chemotherapy is the mainstay of control, but only 4 drugs are available: albendazole, mebendazole, levamisole, and pyrantel pamoate. To assess the efficacy of single-dose oral albendazole, mebendazole, levamisole, and pyrantel pamoate against A lumbricoides, hookworm, and T trichiura infections. A systematic search of PubMed, ISI Web of Science, ScienceDirect, the World Health Organization library database, and the Cochrane Central Register of Controlled Trials (1960 to August 2007). From 168 studies, 20 randomized controlled trials were included. Information on study year and country, sample size, age of study population, mean infection intensity before treatment, diagnostic method used, time between evaluations before and after treatment, cure rate (the percentage of individuals who became helminth egg negative following treatment with an anthelminthic drug), egg reduction rate, adverse events, and trial quality was extracted. Relative risk, including a 95% confidence interval (CI), was used to measure the effect of the drugs on the risk of infection prevalence with a random-effects model. Single-dose oral albendazole, mebendazole, and pyrantel pamoate for infection with A lumbricoides resulted in cure rates of 88% (95% CI, 79%-93%; 557 patients), 95% (95% CI, 91%-97%; 309 patients), and 88% (95% CI, 79%-93%; 131 patients), respectively. Cure rates for infection with T trichiura following treatment with single-dose oral albendazole and mebendazole were 28% (95% CI, 13%-39%; 735 patients) and 36% (95% CI, 16%-51%; 685 patients), respectively. The efficacy of single-dose oral albendazole, mebendazole, and pyrantel pamoate against hookworm infections was 72% (95% CI, 59%-81%; 742 patients), 15% (95% CI, 1%-27%; 853 patients), and 31% (95% CI, 19%-42%; 152 patients), respectively. No pooled relative risks could be calculated for pyrantel pamoate against T trichiura and levamisole for any of the parasites investigated. Single-dose oral albendazole, mebendazole, and pyrantel pamoate show high cure rates against A lumbricoides. For hookworm infection, albendazole was more efficacious than mebendazole and pyrantel pamoate. Treatment of T trichiura with single oral doses of current anthelminthics is unsatisfactory. New anthelminthics are urgently needed.

Immunization against Egyptian &amp;lt;italic&amp;gt;Schistosoma mansoni&amp;lt;/italic&amp;gt; infection by multivalent DNA vaccine

The development of multivalent vaccines consisting of several antigens is a novel approach to creating broad-range protection against different parasite strains and parasite life cycle stages. We have previously confirmed that the schistosome Sm21.7 and SmFimbrin (SmFim) proteins could induce protection in mice. Therefore, this study aimed to construct the multivalent DNA vaccine Sm21.7-SmFim/pBudCE4.1 and evaluate its immune efficacy. The open reading frames of two Schistosoma mansoni genes, Sm21.7 and SmFim, were inserted into the eukaryotic expression plasmid pBudCE4.1 designed for the independent expression of two genes in mammalian cells. To evaluate the in vitro expression of the multivalent Sm21.7-SmFim/pBudCE4.1 DNA vaccine and its immunological effect in mice, the recombinant plasmid Sm21.7-SmFim/pBudCE4.1 was used to transfect 293T cells, and the expression of mRNA and proteins was examined using reverse transcription-polymerase chain reaction and Western blot analysis. Then the ability of Sm21.7-SmFim/pBudCE4.1 to protect against S. mansoni challenge infections was analyzed according to worm burden and egg reduction rates after vaccination of mice. Vaccinated mice showed a significant level of protection (56%), and a decrease in the number and size, and change in the cellular profile, of granulomas. Egg reduction in liver and intestine was 41.53% and 55.63%, respectively, as determined relative to mice that received the empty vector only. In addition to reductions in worm viability, worm fecundity and egg hatching ability were observed following challenge infection in the immunized group. Results showed that Sm21.7-SmFim/pBudCE4.1 could express Sm21.7 and SmFim mRNA and proteins. Enzyme-linked immunosorbent assay and Western blot analysis indicated that immunized mice generated specific immunoglobulin G against Sm21.7-SmFim/pBudCE4.1. These results suggest that vaccination with multivalent S. mansoni DNA vaccine (SmFim-Sm21.7/pBudCE4.1) not only induces a significant reduction in worm and egg burdens, but also significantly reduces the size of egg granulomas. In summary, the multivalent vaccine stimulated specific immunity with a significant level of protection and has anti-pathological effect.

Treatment of intestinal helminthiasis: mebendazole only or mebendazole-pyrantel pamoate?

Background Although intestinal helminthiasis causes highmorbidity and has a negative impact on children’s growth anddevelopment, the efficacy of antihelmintics for multiplehelminthiasis in mass treatment is still doubtful.Objective To compare the efficacy of single dose mebendazoleand a combination of pyrantel pamoate and mebendazole for thetreatment of multiple infections due to Ascaris lumbricoides,hookworm, and Trichuris trichiura.Methods Subjects were elementary school students in Suka Village,Tiga Panah subdistrict, North Sumatera. They were randomizedto either receive mebendazole (M Group) or mebendazole-pyrantel pamoate group (MP Group). Stool examinations wereperfomed on each subjects on day 7, 14, 21, and 28 after treatment.Analyses were perfomed by using chi-squared and Mann-WhitneyU tests.Results The prevalence of intestinal helminthiasis was 95.4%. T.trichiura (88.7%) was the most common cause of infection followedby A. lumbricoides (79.5%), and hookworm (3.1%). Two hundredthirty nine (76.8%) children had multiple infections. Althoughthe egg reduction rate of intestinal helminthiasis in thecombination group was faster than that of the mebendazole group,there was no significant difference in the cure rate of both groups.Conclusion A single dose of mebendazole is preferred for masstreatment of multiple intestinal helminthiasis infections.