Evaluation of the therapeutic efficacy of praziquantel against schistosomes in seven countries with ongoing large-scale deworming programs.

The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic efficacy, measured as the reduction in arithmetic mean of schistosome egg counts following drug administration (egg reduction rate; ERR), was high for all three schistosome species (S. mansoni: 93.4% (95%CI: 88.8-96.8); S. haematobium: 97.7% (95%CI: 96.5-98.7) and S. japonicum: 90.0% (95%CI: 68.4-99.3). At the trial level, therapeutic efficacy was satisfactory (point estimate ERR ≥90%) for all three Schistosoma species with the exception of S. mansoni in Cameroon where the ERR was 88.5% (95%CI: 79.0-95.1). Furthermore, we observed that in some trials individual drug response could vary significantly (wide 95%CI) and that few non-responsive individuals could significantly impact ERR point estimates. In conclusion, these results do not suggest any established reduced efficacy of the standard PZQ treatment to any of the three schistosome species within these countries. Nevertheless, the substantial degree of variation in individual responses to treatment in some countries underpins the need for future monitoring. The reported ERR values serve as reference values to compare with outcomes of future PZQ efficacy studies to ensure early detection of reduced efficacies that could occur as drug pressure continues increase. Finally, this study highlights that 95%CI should be considered in WHO guidelines to classify the therapeutic efficacy of PZQ.

Genetic differences among Haplorchis taichui populations in Indochina revealed by mitochondrial COX1 sequences.

Haplorchis taichui is an intestinal heterophyid fluke that is pathogenic to humans. It is widely distributed in Asia, with a particularly high prevalence in Indochina. Previous work revealed that the lack of gene flow between three distinct populations of Vietnamese H. taichui can be attributed to their geographic isolation with no interconnected river basins. To test the hypothesis that interconnected river basins allow gene flow between otherwise isolated populations of H. taichui, as previously demonstrated for another trematode, Opisthorchis viverrini, we compared the genetic structures of seven populations of H. taichui from various localities in the lower Mekong Basin, in Thailand and Laos, with those in Vietnam, using the mitochondrial cytochrome c oxidase subunit 1 (COX1) gene. To determine the gene flow between these H. taichui populations, we calculated their phylogenetic relationships, genetic distances and haplotype diversity. Each population showed very low nucleotide diversity at this locus. However, high levels of genetic differentiation between the populations indicated very little gene flow. A phylogenetic analysis divided the populations into four clusters that correlated with the country of origin. The negligible gene flow between the Thai and Laos populations, despite sharing the Mekong Basin, caused us to reject our hypothesis. Our data suggest that the distribution of H. taichui populations was incidentally associated with national borders.

Evidence of increasing risk of schistosomiasis among school-age children in municipality of Calatrava, Province of Negros Occidental, Philippines.

OBJECTIVE: To explore risk of school-age children being infected with schistosomiasis in selected villages in the municipality of Calatrava, province of Negros Occidental, Philippines. METHODS: As part of the monitoring and evaluation of the helminth control program in the province of Negros Occidental, parasitological monitoring, through the use microscopy of stool samples processed using Kato-Katz technique, was conducted to describe the baseline and follow-up parasitological status of school-age children in 2010 and 2012, respectively. Seven villages from the municipality of Calatrava were selected as study sites. RESULTS: During baseline assessment, only one case of schistosomiasis was reported from the village of Marcelo. During follow-up assessment, 32 cases (6.9%) of schistosomiasis were reported and the prevalence of moderate-heavy intensity infection was 1.3% in six villages. Among the seven villages included in the follow-up, Minapasuk had the highest prevalence at 14.6%, while San Isidro reported no case of schistosomiasis. CONCLUSIONS: Non-endemic villages, which have reported positive cases in school-age children, may need to be assessed for possible endemicity for schistosomiasis. Transmission of the disease may need to be determined in these villages through active parasitological and malacological surveillance. Other non-endemic villages adjacent to or share river networks with endemic villages in Calatrava may need to be explored for possible introduction of the disease, especially after typhoons and flooding. Establishing endemicity for schistosomiasis in these villages will help infected and at risk individuals to receive yearly treatment to reduce morbidities caused by this disease.

School-based control of soil-transmitted helminthiasis in western Visayas, Philippines.

We evaluated the effect of a local government unit-led, school-based, teacher-assisted mass drug administration (MDA) treatment of soil-transmitted helminthiasis (STH) on the morbidity of school children in selected provinces of western Visayas, the Philippines. Parasitological assessment was done on stool samples using the Kato-Katz technique. Nutritional status and school performance were also evaluated using secondary data from the Department of Education. The overall prevalence of STH decreased from 71.1% to 44.3% (p < 0.0001) and the prevalence of heavy infection with STH decreased from 40.5% to 14.5% (p < 0.0001), after two years of biannual MDA. The prevalence of underweight children decreased from 26.2% to 17.8% (p < 0.0001) and the prevalence of stunted children decreased from 20.9% to 16.6% (p < 0.0001) after two years of biannual MDA. School performance improved on standardized testing from a mean percentage of 53.8% to 64.6%. Advocacy, social mobilization, strong local government support and intersectoral collaboration with other agencies probably contributed to the success of the program.

Field evaluation of malaria rapid diagnostic tests for the diagnosis of P. falciparum and non-P. falciparum infections.

The objective of this study was to evaluate various malaria rapid diagnostic tests as a tool in the detection of P. falciparum and non-P. falciparum infections in field conditions. Four field surveys were conducted in malaria-endemic areas of Palawan and Davao del Norte, Philippines to validate the various rapid diagnostic tests, namely Diamed OptiMAL 48 (DiaMed AG, Switzerland), ParaHIT f (Span Diagnostics, India), Orchid OptiMAL, and Paracheck Pf (both from Orchid Biomedical Systems, India). The results of the various rapid diagnostic tests were compared to those of microscopy. Sensitivity, specificity and detection rates according to the level of parasitemia were used as parameters to describe the performance of the various rapid diagnostic tests in the field. Practical and operational assessments were also done. The results of the study show that the sensitivity and detection rates were generally lower than previously reported, with sensitivities ranging from 4.8% to 20.6%, except for Diamed OptiMAL 48, which had sensitivities of 78.8% to 96.8%, and detection rates of 50.0% to 96.8%. The rest had detection rates ranging from 0.0% to 50.0%. All the specificities ranged from 18.2% to 100.0%. Improper conditions at the time of manufacturing, storage, transport, and utilization may affect the validity of the results. Rapid diagnostic tests for malaria provide practical means of detecting malarial infections, especially in endemic areas. However, issues regarding variability in performance must to be addressed before they can be used as mainstream diagnostic tools.

A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp.

OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems.

Intestinal heterophyidiasis: an emerging food-borne parasitic zoonosis in southern Philippines.

Heterophyidiasis is an infection of the small bowel by minute intestinal flukes of the genus Heterophyes or related members of the family Heterophyidae. To provide a better understanding of this rarely reported condition, this study attempted to determine the infection rate, intensity of infection as well as the clinical spectrum of heterophyid infection. A stool survey was conducted in barangay San Isidro, Monkayo, Compostela Valley. Thirty-six percent of patients with history of bowel disturbance (abdominal discomfort/pain and/or diarrhea) in the past 4 weeks were found to have heterophyidiasis. All age groups were infected, with the youngest patient being 1 year 7 months of age, while the oldest patient was 73 years of age. Prevalence was highest in the 15 to 30 years old group at 55.3%. The most common clinical manifestations of heterophyidiasis were signs and symptoms of acid peptic or peptic ulcer disease. Early diagnosis and treatment are important to ensure prompt resolution of heterophyid infection, hence, decreased morbidity and decreased chances for complications like heart or brain involvement. Proficiency of laboratory staff should be enhanced to ensure accurate diagnosis which will then make appropriate treatment possible.

Compostela Valley: a new endemic focus for Capillariasis philippinensis.

A 20 year old female from Compostela Valley Province in the Philippines, presenting with chronic diarrhea, borborygmi, bipedal edema, anorexia and weight loss was seen at Davao Regional Hospital. Her stool specimen, suspected by a local medical technologist to have Capillaria philippinensis ova, was forwarded to the Diagnostic Parasitology Laboratory of the College of Public Health, University of the Philippines Manila. It was examined and found to contain Capillaria philippinensis adults, larvae and eggs. Twelve deaths among people coming from the same barangay, affected by a similar illness with no definite diagnosis except "gastroenteritis" were also reported. These prompted health officials to send a team that would investigate the etiology of the disease outbreak labeled as a "Mystery Disease". Seventy-two stool samples from symptomatic patients were examined. Fifty-three (73.6%) individuals were proven to harbor at least one parasite with 16 (22.2%) individuals positive for Capillaria philippinensis infection. Ocular inspection, interviews and focus group discussions revealed that the people's eating habits are not much different from the habits of those from the Ilocos provinces where capillariasis was initially described. In both areas, people are fond of eating kinilaw or raw fish. They also eat raw shrimps, crabs and snails. Furthermore, the people defecate in the field or in the same body of water where they get the fishes, shrimps, crabs and snails that they eat, thus completing the life cycle of Capillaria philippinensis. Fish-eating birds were likely to have spread this parasite to the area. This is the first report of a capillariasis outbreak in Compostela Valley Province, and this should alert health authorities to consider embarking on serious efforts for developing proficiency of laboratory and clinical diagnosis especially in government health facilities where the poor and marginalized sectors of society are likely to consult.

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Immunoglobulin allotypes among the Bicolanos of Sorsogon province, Luzon, Philippines: implications of phenotypes for filariasis.

Immunoglobulin (Ig) allotypes are polymorphic genetic systems that show distinct racial arrays, thus making them powerful tools for studies of genetic admixture and biological relationships. In the province of Sorsogon, southern Luzon, Philippines, allotyping was completed on 252 persons residing in two neighboring villages. The people demonstrated 14 GM and 3 KM phenotypes. The frequency of homozygous KM3, KM1 and heterozygous KM1,3 was identical in these villages; however, half of the GM phenotypes present in one village were significantly less frequent in the other village. The frequency of KM and GM haplotypes was different from those reported in Filipino aboriginal groups, but similar to a population on Samar Island, the only other Filipino group for which Ig allotype data exist. Variability in the prevalence of parasitic disease such as lymphatic filariasis may in part reflect differences in genetic susceptibility, resulting from allotypic heterogeneity between villages.

Vector abundance and behaviour in an area of low malaria endemicity in Bataan, the Philippines.

The vectorial importance of known and potential vectors in Morong, Bataan, Philippines was assessed based on human and animal baited collections of adult mosquitoes and on larval collections. Anopheles flavirostris, the principal vector in the Philippines, was the most abundant among human landing catches, followed by An. maculatus sensu lato (s.l.). Both showed similar seasonal abundance with a peak during the early drier part of the year, which coincided with the peak in malaria cases. Both An. flavirostris and An. maculatus s.l. fed throughout the night with the broad peak of capture from 00:00 to 04:00 and from 22:00 to 00:00, respectively. The two species had similar parous rates (0.76 and 0.72, respectively) giving an average life span equivalent to four feeding cycles. Neither vector was abundant with average human landing rates on collectors of 0.6 and 0.4 mosquitoes per person per night, respectively over the study period. An. maculatus s.l. showed a stronger preference for outdoor feeding compared to An. flavirostris. An. maculatus s.l. was markedly zoophilic with a biting rate on water buffalo 50 times the human landing rate. An. flavirostris was less zoophilic with a corresponding ratio of 7.5. It was concluded that in this area, An. flavirostris is the principal vector. The combination of localised transmission, late night biting pattern and localised breeding sites of An. flavirostris suggest that the use of bed nets and environmental management are relevant control measures that can be implemented through community participation.

Field epidemiological studies on malaria in a low endemic area in the Philippines.

Field epidemiological studies were conducted to examine factors affecting endemicity in an area with a low prevalence of malaria. Two annual cross sectional surveys were done to estimate parasite prevalence rates at two periods in time, to determine the distribution of the parasitemic population and to describe the serological status of the population. A longitudinal study of a sample of infected people was used to measure reinfection rates and antibody dynamics. A 2 year passive case detection was done to estimate the number and distribution of people with symptomatic infections. Malaria was found in all age groups, with marked clustering of cases. Active and passive case detection and serological surveys all gave a similar pattern of malaria distribution: generally low prevalence with small foci of relatively high endemicity. The infection frequencies were generally similar in all age groups, measured by both active and passive case detection. There was a high frequency of P. falciparum gametocytemic infections in the asymptomatic cases found through active case detection. Twenty to 39 year old males had the highest frequency of infection by active case detection, and 10-19 year old males by passive case detection. These two groups were also more likely to be gametocyte positive than their female counterparts, suggesting that in this community, this portion of the population acts as the main reservoir of infection.

Risk factors for infection with malaria in a low endemic community in Bataan, the Philippines.

The patterns of malaria morbidity and mortality can vary with the level of malaria transmission in a given area. We carried out two annual cross-sectional surveys in the hypoendemic malarious community of Morong, the Philippines, to examine epidemiologic and sociobehavioural risk factors for infection. In both surveys, the greatest risk of having malaria was associated with place of residence. For example, in the first survey, living in an area where more than 50% of the community had a high IFAT titer had an adjusted odds ratio (OR) of 33.7. A range of activities thought to be associated with risk were examined, but in the first survey, only frequent nocturnal visits to the forest were found to be a significant risk factor overall (adjusted OR; 2.65; 95% CI 1.48, 4.73), but this phenomenon was primarily observed among individuals residing in the lowest prevalence areas. In the second survey, where only the area with a relatively high prevalence of malaria was sampled, no association with activities was found. In this survey, significant factors associated with malarial infection were: being a migrant (adjusted OR 1.97; 95% CI 1.33, 2.92), being male (adjusted OR 1.63; 95% CI 1.10, 2.43) and age 30 years or less (adjusted OR 0.29 for age > 30 years; 95% CI 0.16, 0.52). The data suggest that in low-endemic communities like Morong, Bataan, control efforts should be primarily directed to focal areas identified by serology, particularly among migrants and among male young adults.

Stability of malaria in a community in Bataan, the Philippines: prospects for control.

Malaria in Morong, Bataan, The Philippines, a municipality with relatively low level, but stable malaria is associated with small foci of relatively high endemicity. Although there is little association between age and symptomatic malaria, there is a reservoir of asymptomatic cases which are present throughout the year. Risk analysis suggests that the greatest risk factor in acquiring malaria depends on place of residence and not on occupation, including those associated with forest activities such as charcoal making. Foci of infection and the timing of symptomatic cases is closely correlated with breeding sites and abundance of adult Anopheles flavirostris. In spite of this close association, widely held views in the community that malaria is not related to mosquito transmission are likely to make better malaria control based on vector control difficult to sustain. Observation of treatment practices in the community and estimates of the number of apparently asymptomatic carriers from active case detection illustrate the importance of delayed treatment in providing a continuing reservoir of infection. These results highlight the need for improved early case detection and treatment.

Pulmonary paragonimiasis and tuberculosis in Sorsogon, Philippines.

The clinical epidemiology of pulmonary paragonimiasis and tuberculosis was investigated in a known endemic municipality of Sorsogon, Philippines. Records of diagnosed tuberculosis patients on treatment and follow up at the local Rural Health Unit over a two year period from 1993 to 1994 were reviewed to provide an overview of pulmonary tuberculosis in the area, specifically to describe the population at risk, the basis for diagnosis and the proportion of case notification who were sputum negative. Patients from the same group of individuals as well as undiagnosed tuberculosis patients with productive cough, fever with chest and/or back pain, or hemoptysis were examined to look into clinical manifestations, duration of symptoms, history of crab-eating and sputum examination results for acid-fast bacilli and Paragonimus. There was difficulty in determining the number of non-responders as the records did not have any provision for the recording of such. Annual tuberculosis case notification rates for the two years (374 and 401 per 100,000 population) were higher than the national figure in 1991 (325 per 100,000 population) indicating that tuberculosis is still a major health problem in the area and tuberculosis control efforts may have to be more aggressive to better contain the disease. Twenty-six out of 160 individuals surveyed were sputum smear positive for Paragonimus. Paragonimiasis rates were not significantly different in the two groups (15.6% vs 16.9%, respectively) indicating that there is a need for routine sputum examination for Paragonimus which is not available at present. Only six patients surveyed were sputum smear positive for acid-fast bacilli. A high index of suspicion is necessary to diagnose paragonimiasis and to be able to differentiate it from tuberculosis. The diagnosis may be suggested by a patient's place of origin being a known endemic area, a long period of chronic cough and the habit of eating raw or insufficiently cooked crabs or crayfish. Laboratories in endemic areas should have the capacity to differentiate between the two infections by being able to provide the routine laboratory procedures necessary for definitive diagnosis and treatment.

Problems with filariasis control in the Philippines.

Problems with filariasis control in this country of more than seven thousand islands are presented and discussed according to the political, economic, and socio-behavioral aspects. Discussed are issues relating not only to the recipients of the health services and control programs but also to the people in the control program and disease control managers. Marinduque, a recently described endemic focus of lymphatic filariasis, is used to illustrate the many problems affecting the control efforts in the Philippines. The true impact of the problem has not been described lately, hence the need for epidemiologic, social, and economic impact studies.