Accuracy of the health information system on malaria surveillance in Vietnam.

The health information system (HIS) is a key component of control programs and its accuracy is necessary for the assessment of disease risks, the formulation of priorities and the evaluation of the cost-effectiveness of different interventions. In order to assess the quality of the HIS in estimating malaria morbidity in Vietnam, we compared data obtained by a 2-year active (ACD) and passive case detection (PCD) study with those routinely collected at the local commune health centres (CHC) at three sites having different malaria epidemiology. The majority of malaria cases (80-95%) detected by ACD were missed by the HIS. Similarly, most malaria cases (50-90%) detected by PCD were also missed by the HIS, and this was proportional to the number of active private practitioners. Reasons for this low sensitivity are low CHC attendance, high attendance at private health facilities, widespread self-medication and attendance at central health facilities. In conclusion, although malaria has sharply decreased in Vietnam over the past 10 years, the current HIS greatly underestimates the malaria burden. Involvement of the private sector and the establishment of sentinel sites might improve the quality of data and the relevance of HIS in malaria control.

Malaria epidemiology in a rural area of the Mekong Delta: a prospective community-based study.

Over the past 10 years, the Mekong Delta region in Vietnam has experienced fast socio-economic development with subsequent changes in malaria vectors ecology. We conducted a 2-year prospective community-based study in a coastal rural area in the southern Mekong Delta to re-assess the malaria epidemiological situation and the dynamics of transmission. The incidence rate of clinical malaria, established on 558 individuals followed for 23 months by active case detection and biannual cross-sectional surveys, was 2.6/100 person-years. Over the 2-year study period, the parasite rate and malaria seroprevalence (Plasmodium falciparum and P. vivax) decreased significantly from 2.4% to almost 0%. Passive case detection (PCD) of clinical cases and serological follow-up of newborns carried out in a larger population confirmed the low and decreasing trend of malaria transmission. The majority of fever cases were seen in the private sector and most were unnecessarily treated with antimalarials. Training and involvement of the private sector in detection of malaria cases would greatly improve the quality of health care and health information system.

Malaria transmission and major malaria vectors in different geographical areas of Southeast Asia.

During the last decade, major progress in malaria control has been achieved in Vietnam, Laos and Cambodia. However, malaria is still a potentially fatal disease in some hilly-forested areas and continues to be endemic in a few coastal foci. To estimate the risk that stems from the major vectors after a decade of intensive malaria control, an entomological study based on human landing collections was conducted between April 1998 and November 2000 in six study villages (four in Vietnam, one in Cambodia and one in Laos) located in different physio-geographical areas. Five villages were selected in places where new cases of malaria still occurred. In the sixth village, in the northern hilly area of Vietnam, no case of malaria was detected during the past 3 years. In three study villages of the hilly forested areas of Cambodia and central Vietnam, Anopheles dirus A still played an important role in malaria transmission and maintain perennial transmission inside the villages despite its low density. Anopheles minimus A was found in all study villages except in the southern coastal village of Vietnam. Its role in malaria transmission, however, varied between localities and surveys. In one study village of central Vietnam it was almost absent (one specimen collected over 480 man nights), and in another village sporozoite positive specimens (2.8%) were only observed during the first two surveys whereas this species disappeared from the collections from November 1998 onwards (six surveys: 360 man nights). In the northern study site An. minimus A and C were found in all collections, but no local malaria transmission occurred. However, the constant presence of these two species associated with a high longevity (parous rate up around 80% and 65%, respectively), suggests that transmission can occur at almost any time if parasite reservoirs are reintroduced in the area. The proper management of malaria cases and population movement is, therefore, important to prevent outbreaks and the reintroduction of malaria in northern Vietnam. In the study site of the Mekong delta, An. sundaicus occurred at high densities (up to 190 bites/man/night). The recent changes in land use from rice cultivation to shrimp farming probably explains the increase of this brackish water breeding species during the study period. However, none of the 11,002 specimens was positive for Plasmodium circumsporozoite protein (CSP). The relative low survival rate as estimated by the parous rate (around 47%) may reflect its low vectorial status that could explain the very low malaria incidence (1.9 case/100 persons/year) in this study site. A calculated sporozoite rate of maximum 1/300,000 is enough to explain this low malaria incidence. Despite the successes in malaria control, the vector An. dirus A continues to play an important role in malaria transmission, whereas An. minimus A showed temporal and spatial variation in its role as vector. The role of An. sundaicus as vector could not be confirmed because of the low incidence in the coastal study village. Other Anopheles species may be locally involved, but in the five study villages where malaria is still present they probably do not contribute significantly to malaria transmission. The study also points towards the fact that in Southeast Asia it will become increasingly difficult to incriminate Anopheles species in malaria transmission while the risk for malaria transmission still persist.

Assessment of susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine, sulfadoxine-pyrimethamine and artemisinin in southern Viet Nam.

Resistance to antimalarial chemotherapy is a major concern for malaria control in Viet Nam. In this study undertaken in 1998, 65 patients with uncomplicated Plasmodium falciparum malaria were monitored for 28 days after completion of a 5-day treatment course with artemisinin. Overall 36.9% (24/65) of patients had recurrent parasitaemia during the surveillance period. P. falciparum isolates were tested for sensitivity in vitro to chloroquine, mefloquine, quinine, sulfadoxine-pyrimethamine and results were compared to those from a similar study in 1995. Increased parasite sensitivity to sulfadoxine-pyrimethamine, chloroquine and quinine was demonstrated, with significantly lower mean EC50 and EC99 values in 1998 compared to 1995. Parasite sensitivity to mefloquine did not differ significantly in the 2 surveys. Isolates were also tested for sensitivity in vitro to artemisinin in the 1998 survey. The mean EC50 was 0.03 mumol/L and the EC99 was 0.94 mumol/L. Parasite sensitivity to artemisinin will need to be monitored in view of its increasing use in Viet Nam.

Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro.

To assess the antimalarial sensitivity of Plasmodium falciparum in vivo and in vitro in a highly endemic area of southern Viet Nam, a field study was conducted (in 1999) at a rubber plantation in Binh Phuoc Province north of Ho Chi Minh City. Fifty patients were treated with either artesunate (4 mg/kg on day 0, then 2 mg/kg on day 1 to 4) or mefloquine (10 mg/kg at 0 h, then 5 mg/kg at 6 h), and their progress was followed for 28 days under standard WHO protocols. Blood spots were taken at baseline from all patients, as well as from those who redeveloped parasitaemia during follow-up, for polymerase chain reaction (PCR) determination of parasite genotypes to assist differentiation of re-infection from recrudescence. Both treatments cleared parasites within 5 days. Of the 25 mefloquine-treated patients, 2 (8%) re-presented with probable re-infections. For artesunate, 4 patients (16%) had re-infections and 5 (20%) had recrudescences. Sensitivity tests in vitro of pre-treatment P. falciparum isolates showed geometric mean IC50 values of 29, 38, 209 and 15 nmol/L for chloroquine (n = 32), mefloquine (n = 33), quinine (n = 31) and artemisinin (n = 31), respectively. There were significant correlations between IC50s for artemisinin and mefloquine (r = 0.72, P = 0.004), and chloroquine and quinine (r = 0.44, P = 0.05). These data show that, although mefloquine has been used for 10 years in Binh Phuoc Province, it remains fully effective, perhaps because an artemisinin derivative is commonly given at the same time. The recrudescence rate for artesunate is similar to those reported in other epidemiological contexts. The present in-vitro data imply that quinine remains effective and that reduced drug pressure has been associated with increased sensitivity of local strains of P. falciparum to chloroquine. Although from one hyperendemic area, these results may have implications for antimalarial prophylaxis and treatment strategies for residents and travellers to southern Viet Nam.

Epidemiology, symptoms and treatment of paragonimiasis in Sin Ho district, Lai Chau province, Vietnam.

Sin Ho is a district of the northern mountainous province of Lai Chau, Vietnam, where the people have the habit of eating undercooked crabs. A study on paragoniamiasis carried out from 1994 to 1995 with 1,642 persons in this endemic area, showed that the rate of eating raw-crab was 72.5%. Crab examination (Ranguna kimboiensis) showed an infection rate of Paragonimus metacercaria of 98.1%. With 624 stool samples examined by Kato technique, the infection rate of Paragonimus in humans was 6.4%. With 338 sputum samples examined by direct and centrifuge methods, the infection rate of Paragonimus was 7.4%. Most of the patients were children (63.2%). The infection rate of Paragonimus in dogs was 18.2 - 33.3%. Adult worms, collected from the dogs in the field and from the cats in laboratory, were identified as Paragonimus heterotremus. The main symptoms of Paragonimus patients were cough and hemoptysis (92%), discontinuously developed (96%), without fever (94%), chest pain (70%), pleural effusion (26%), neurogical symptoms (8%), eosinophilia (88.9%), nodular ring shadows in the lungs, as shown by chest X-ray examination and more in lower lobe, (76.2%). Paragonimiasis patients were treated by (a) Praziquantel 25 mg/kg/day x 3 days; the cure rate was 68.8%. (b) Praziquantel 50 mg/kg/day x 3 days; the cure rate was 75%.

Epidemiology of soil-transmitted nematode infections in Ha Nam Province, Vietnam.

Baseline epidemiological data are presented from a parasitological survey conducted in Thuy Loi commune, Ha Nam province, Vietnam; a farming community where night soil is routinely used as fertilizer for crops. 177 households were visited and 543 individuals (aged 1-88 years) recruited to the study. Helminth infection intensity was assessed by Kato-Katz to determine the density of parasite eggs per gram of stool (epg). Ascaris lumbricoides, Trichuris trichiura and hookworm infections were the only species detected. 83% of individuals were infected with A. lumbricoides (mean epg = 11,971), 94% with T. trichiura (mean epg = 793) and 59% with hookworm (mean epg = 302). Age-dependent patterns of infection prevalence and intensity were similar for A. lumbricoides and T. trichiura, but markedly different for hookworm infection. Similarly, age-dependency in the k-values for the three infections was due to covariance with the respective mean intensities with age rather than to independent age effects, with similar patterns for A. lumbricoides and T. trichiura, and a different pattern for hookworm. Three major conclusions can be drawn from the multiple-species analyses: There is positive interaction between A. lumbricoides and T. trichiura infections; high-intensity A. lumbricoides infections are significantly associated with high-intensity T. trichiura infections; and there is positive interaction between these two species such that infection intensity of A. lumbricoides is higher in individuals with concurrent T. trichiura infection than in individuals without and vice versa.

Use and quality of antimalarial drugs in the private sector in Viet Nam.

This study examines the use and quality of antimalarial drugs in the growing private sector of Viet Nam. The practices of drug vendors (called alternative treatment providers (ATPs)) as well as their stocks and the quality of drugs sold by them, and the local production and distribution of antimalarials were investigated. Antimalarials were sold by the vast majority of ATPs, almost all the common antimalarials being available for sale. The practices and indications for sale, however, varied. Underdosing for malaria was frequent in all three provinces studied, and lack of knowledge of the appropriate regimen for cure was common among the drug-sellers. Samples of antimalarials were collected from ATP outlets in the three provinces, and the drugs were assessed for their contents and expiry date by the Institute of Drug Quality Control in Hanoi. Of the 218 samples of drugs examined by the Institute, over 96% met the quality requirements. However, a 10% sample of these drugs were independently assessed by WHO and revealed a different picture: 70% of them failed to meet the standard specifications required. There is therefore an urgent need to improve the capability and monitoring procedures of bodies involved in assessing and regulating drugs in Viet Nam.

Artemisinin population pharmacokinetics in children and adults with uncomplicated falciparum malaria.

AIMS: To investigate the pharmacokinetics of the antimalarial artemisinin in the field setting using sparsely collected data. METHODS: Artemisinin concentrations were determined by h.p.l.c. in a total of 107 capillary plasma samples collected on the first day and in 33 samples on the last day of a 5-day oral artemisinin regimen of 10 mg kg(-1) day(-1) in 23 paediatric (aged 2-12 years) and 31 adult (aged 16-45 years) Vietnamese patients with uncomplicated falciparum malaria. The population model was developed using NONMEM, incorporating interoccasion variability and accounting for a systematic change in artemisinin pharmacokinetics with time, modelled as a change in oral bioavailability. RESULTS: Clinical efficacy, in terms of parasite clearance and fever subsidence times, was comparable between children and adults. A one-compartment model with separate pharmacokinetic estimates for children and adults was found best to describe the disposition of artemisinin after oral administration. The population estimates for artemisinin clearance and distribution volume, respectively, were 432 1 h(-1) and 16001 for adults and 14.41 h(-1) kg(-1) and 37.91 kg(-1) for children, with an intersubject variability (collectively for both age groups) of 45% and 104%, respectively. The oral bioavailability was estimated to decrease from Day 1 to Day 5 by a factor of 6.9, a value found to be similar for children and adults. CONCLUSIONS: Artemisinin pharmacokinetic data was successfully derived in both paediatric and adult patients using 2-3 capillary blood samples taken in conjunction with parasitaemia monitoring. This study's findings advocated the dosing of artemisinin to children according to bodyweight and to adults according to a standard dose.

Artemisinin pharmacokinetics is time-dependent during repeated oral administration in healthy male adults.

The pharmacokinetics of the antimalarial artemisinin exhibited an unusual time dependency during a 7-day oral daily regimen of 500 mg in 10 healthy, male Vietnamese adults. Artemisinin areas under the plasma concentration-time curve (AUC) decreased to 34% (median) by day 4 with a further decrease by day 7 to only 24% of values obtained after the first day of administration. In seven subjects restudied after a 2-week washout period, artemisinin AUCs had almost normalized, demonstrating the reversibility of the time-dependent drug disposition. The results suggest artemisinin exhibits an auto-inductive effect on drug metabolism of an unusual magnitude. This may partly explain why some patients on standard doses, due to subparasiticidal drug levels toward the end of a standard regimen, do not completely clear parasites. Further, the possibility of drug-drug metabolic interactions during combination regimens is implicated.

Epidemiology of clonorchiasis in Ninh Binh Province, Vietnam.

Clinical and stool examinations for clonorchiasis were carried out in an endemic area, Kim Son District, Ninh Binh Province, Vietnam. Stool examination with the Kato-Katz technic revealed that in 306 residents selected randomly, 42 people (13.7%) were infected with Clonorchis sinensis. The rate was biased towards men (23.4%) as opposed to women (1.5%) and increased with age. No children younger than 10 years old were infected, reflecting difference in a chance for acquisition of infection through a habit of eating raw fish. Few clinical abnormalities were found by blood and urine examinations of the patients. Treatment with praziquantel decreased the infection rate to 5.3% at 6 weeks later. Snails, Melanoides tuberculatus, collected from ponds around the settlements were infected with cercariae at a rate of 13.3%. Farmed fish (Hypophthalmichtys molitrix) in the ponds were infected with metacercariae at rates of 56.4% in small individuals and 100% in large ones. The life cycle of C. sinensis is exclusively completed in the ponds and the traditional habit of eating raw fish in summer was thought to be a major route of infection.