Risk Associated with Malaria Infection in Tihama Qahtan, Aseer Region, Kingdom of Saudi Arabia: 2006-2007.

INTRODUCTION: Since 2004, the Kingdom of Saudi Arabia has pursued a policy of malaria elimination. The distribution of malaria at this time was constrained to regions located in the South Western part of the country. The present study aimed to understand the risk of malaria infection and factors associated with these events between March 2006 and August 2007 in one part of Aseer region. METHODS: The study was carried out in Tihama Qahtan area in the far southeastern part of Aseer, historically the most malaria endemic area of this region. The area covers 54 villages served by three primary health care centres (Wadi Alhayah, Alfarsha and Albuqaa). Malaria cases were detected using passive case detection (PCD) at the three health centres for 18 months from March 2006, each positive case was investigated using patient and household level enquiries. In addition, four cross-sectional surveys in 12 villages were undertaken using rapid diagnostic tests within the catchments of each health centre coinciding with malaria transmission seasons. RESULTS: Among 1840 individuals examined in the PCD survey, 49 (2.7%) were positive for malaria, most were Plasmodium falciparum cases and one was a P. vivax case. The majority of these infections were likely to have been acquired outside of the area and represent imported cases, including those from the neighboring region of Jazan. Among the 18 locally acquired cases, the majority were adult males who slept outdoors. 3623 individuals were screened during the cross-sectional surveys, 16 (0.44%) were positive and infections only detected during peak, potential transmission periods. CONCLUSION: There was evidence of local malaria transmission in the Tihama Qahtan area in 2006-2007, however prevalence and incidence of new infections was very low, making the future ambitions of elimination biologically feasible. The constant source of imported infections must be considered in the area's elimination ambitions, alongside strong behavioural community messages about sleeping outdoors unprotected and travel to malaria endemic areas outside the region.

Injection safety at primary health care level in south-western Saudi Arabia.

In a study of injection safety in Abha health district, Saudi Arabia, data were collected from 47 physicians and 85 nurses at 24 primary health care centres, using an observation checklist and an interview questionnaire. All centres used individually packed disposable syringes and puncture-proof containers to collect used needles. Needlestick injury in the previous year was reported by 14.9% of physicians and 16.5% of nurses (0.21 and 0.38 injuries/person/year respectively). Logistic regression analysis identified recapping the needle after use (physicians and nurses) and bending the needle before disposal (physicians) as significant risk factors for injury.

Primary health care emergency services in Abha district of southwestern Saudi Arabia.

To study emergency services delivery in all 30 primary health care centres in Abha district of Asir region, Saudi Arabia, data were collected about equipment and facilities, physicians' practices and attitudes, and patients' utilization of and satisfaction with emergency services. Two centres had no devoted place for emergency services. Lack of some essential equipment and drugs was evident. The greatest continuing medical education need for doctors was the management of cardiovascular emergencies (72.3%). Many doctors (40.4%) did not consider the majority of cases as true emergencies. Many patients (43.7%) used the centres for emergency services, the most common being trauma, burns and orthopaedics (47.8%). Most patients were satisfied overall with emergency services (82.2%).

Specific immunoglobulin measurements related to exposure and resistance to Schistosoma mansoni infection in Sudanese canal cleaners.

The present work comprises a longitudinal study of Schistosoma mansoni infection in occupationally hyper-exposed canal cleaners in the Sudan and the influence of chemotherapy on humoral immune parameters. The study groups included chronically infected canal cleaners (n = 19), newly recruited canal cleaners (n = 17), normally exposed adults (n = 31), school children (n = 46) and Sudanese negative controls (n = 48). Previous studies of the same canal cleaners have demonstrated that chronically infected canal cleaners were more resistant to reinfection than newly recruited canal cleaners. ELISA was used to detect specific IgE and IgG subclasses in response to whole worm antigen (WWH) and soluble egg antigen (SEA) before and 3 months after praziquantel treatment in the groups of canal cleaners and before and 1 year after treatment in normally exposed adults. When intensity of infection was correlated with IgE antibody response, the resistant group of canal cleaners (those who stopped passing ova after treatment) showed a significant positive correlation between intensity of infection and specific IgE to WWH (Spearman's correlation coefficient = 0.49, P < 0.05) compared with a highly significant negative correlation in the susceptible group (acquired new infection after treatment, Spearman's correlation coefficient = -0.94, P < 0.01). Normally exposed adults and school children had significantly less specific IgE to WWH than canal cleaners, while chronically infected canal cleaners had significantly higher levels of specific IgG1 to WWH than newly recruited canal cleaners and school children, and significantly higher levels of specific IgG4 to WWH than school children. There was a significant increase in specific IgG1 and IgG4 to WWH, 3 months after treatment, in newly recruited canal cleaners and a significant decrease, 1 year after treatment, in normally exposed adults. None of the groups studied after treatment showed a significant change in their specific IgE to WWH. Normally exposed adults had significantly lower levels of specific IgE to SEA than newly recruited canal cleaners, and significantly lower levels of specific IgG1 to SEA than other infected groups. Both newly recruited canal cleaners and school children had significantly higher levels of specific IgG2 to SEA than persons in other groups. Only small differences between groups were observed with regard to specific IgG3 and IgM to SEA. Specific IgG4 to WWH and SEA showed different patterns after treatment between the resistant and susceptible groups of canal cleaners. The resistant group maintained the same level of IgG4 to WWH after treatment compared with a significant increase in the susceptible group. On the other hand, levels of specific IgG4 to SEA showed a highly significant decrease after treatment in the resistant group. In contrast, the same antibody subclass increased after treatment in the susceptible group. Generally, results show an association between IgE and IgG1 responses to WWH and resistance to reinfection. In contrast, an association was observed between IgG2 and IgM responses to SEA and susceptibility to reinfection.

Infection and transmission pattern of Schistosoma mansoni in the Managil irrigation scheme, Sudan.

The endemicity (prevalence, intensity and incidence) of schistosomiasis mansoni and its patterns of transmission (focality, seasonality) were studied in five villages in the Managil irrigation scheme, Sudan. Marked differences between villages were observed in overall prevalence (33.3%-54.8%), intensity (77.3-135.0 eggs/g faeces), incidence (15.2%-57.9%) and age-related patterns of Schistosoma mansoni infections. Overall, prevalence and intensity of infection peaked in those aged 10-14 years and then declined slowly with increasing age. However, there were second, smaller peaks in both prevalence and intensity of infection in the older males (> 40 years) and, in general, the indices of infection for males exceeded those for females. The infection pattern was influenced by occupation and possibly by having a latrine. Transmission of S. mansoni in the Managil irrigation scheme is highly focal and seasonal, taking place in a few major human-contact sites near villages and peaking during the hot and dry season (April-June). The infection and transmission patterns of S. mansoni in the scheme show great resemblance to those in the neighbouring Gezira irrigation scheme.

Evaluation of focal mollusciciding in the Rahad Irrigation Scheme, Sudan.

Since the establishment of the Rahad Irrigation Scheme in 1979, the prevalence of schistosomiasis has increased to high levels in some villages despite the efforts of the Blue Nile Health Project to prevent this. Although a programme of focal snail control has been implemented since 1979, when the first intermediate host snails were detected, infected snails are abundant in human water contact near villages where transmission of both S. mansoni and S. haematobium takes place. The objective of the present study was to assess the feasibility and effectiveness of the focal snail control operations in irrigation canals, in terms of reductions in snail density and repopulation rates of treated sites. The efficacy of focal mollusciciding was evaluated by (1) evaluation of the routine molluscicide operation done by the Blue Nile Health Project, (2) experimental application of various dosages of the molluscicide and (3) study of snail repopulation rates. Efficiency was measured by mortality among caged snails placed in the target stretch and from pre- and post-treatment counts of relative snail densities. The short-time application of niclosamide can be very effective in reducing the density of the intermediate host snails in the target stretch of canal. An efficient exposure seems to be approximately 3 ppm (a.i.) for 30-40 min when water flow is slow, while 1 ppm is efficient when water velocity is very slow, i.e. less than 0.04 m S-1, and 0.6 ppm is efficient when the water is virtually stagnant. Turbidity seems not to impair the effect of the treatment and vegetation does not reduce the efficiency of niclosamide, provided the current speed is low and the chemical is applied to the entire width of the canal. However, the results also clearly demonstrate some of the shortcomings of the standard procedure of niclosamide application. A high water velocity and discharge will rapidly wash the chemical through the target canal stretch and the snails will be exposed only for a short period if the routine procedure is followed. In addition, the chemical will not mix sufficiently with water within standards of aquatic macrophytes. Recolonization of treated canal stretches is fast, especially during the irrigation period when water velocities are high and juvenile snails are abundant. Snail density may attain pretreatment levels three weeks after an effective application. Since the routine procedure is most effective at low current speeds, it is suggested that water velocity could be controlled during the application in coordination with the Irrigation Department.

Immune response in chronic Schistosomiasis haematobium and mansoni. Reversibility of alterations after anti-parasitic treatment with praziquantel.

Peripheral blood mononuclear cells from Sudanese children heavily infected with Schistosoma haematobium and S. mansoni were examined for lymphocyte subpopulations, for mitogen and antigen responsiveness, and for natural killer (NK) cell activity before and 5 months after treatment with praziquantel. The humoral immune response was simultaneously investigated by determination of parasite-specific IgG and IgE antibodies, IgE-containing circulating immune complexes, and circulating schistosome antigen. A single dose treatment with praziquantel (40 mg/kg) resulted in a normalization of numerical imbalances in lymphocyte subpopulations, a significant increase in the blastogenic response upon stimulation with adult worm antigen, phytohaemagglutinin (PHA), and concanavalin A (Con A), and restoration of natural killer (NK) cell-mediated lysis of K562 targets. These findings were paralleled by a remarkable decrease in parasite-specific IgE antibodies, IgE-containing circulating immune complexes, and circulating schistosome antigen. The results indicate that the modulation of immune responses in chronic schistosomiasis is associated with active infection and is reversible after successful chemotherapy.

Efficacy and tolerance of praziquantel in patients with Schistosoma mansoni infection and Symmers' fibrosis: a field study in the Sudan.

Ultrasonography was used in a village in the Gezira-Managil scheme in the Sudan to identify patients with Symmers' fibrosis. In a random sample from patients with active Schistosoma mansoni infection, 238 patients were found to have no liver involvement while 59 had Symmers' periportal fibrosis. Patients were treated with a single dose of 40 mg/kg body weight of praziquantel. Six months after dosing, 51% and 58% were cured of the infection with 81% and 84% reduction in egg burden in the Symmers' and non-Symmers' patients, respectively. The drug was equally well tolerated by the two groups. It is concluded that patients with Symmers' fibrosis respond to praziquantel and tolerate the drug in a similar manner to patients without Symmers'.

Praziquantel and oltipraz: the treatment of schoolchildren infected with Schistosoma mansoni and/or Schistosoma haematobium in Gezira, Sudan.

Of 111 schoolchildren--all of whom were infected with Schistosoma mansoni and 97 of whom were also infected with S. haematobium--54 were treated with Praziquantel (2 x 20 mg kg-1) and 57 with Oltipraz (2 x 15 mg kg-1). There was no apparent difference between the efficacy of the two drugs. Follow-up studies over the following 12 months indicated that mass chemotherapy of schoolchildren can be expected to reduce the egg output of those treated by almost 100%, but that, unless there is some break in transmission, the egg output may well be as high after 12 months as it was before treatment--at least in the boys. After a round of chemotherapy, retreatment of school-aged boys in an area where transmission is heavy will be necessary six to 12 months later.

Human schistosomiasis: deficiency of large granular lymphocytes and indomethacin-sensitive suppression of natural killing.

Twenty-eight children infected with Schistosoma haematobium and S. mansoni were tested for natural killer (NK) cell activity in vitro using the myeloid/erythroid cell line K562 as target. In addition, the frequency of large granular lymphocytes (LGL) and the number of HNK-1+ lymphocytes were examined in peripheral blood. NK cell activity was found to be markedly reduced in most patients when compared with a group of healthy Caucasian individuals (P less than 0.005). Moreover, the impairment of NK activity clearly correlated with the intensity of infection, which was quantified by parasite ova excretion in stool and urine. Within the lymphocyte compartment the percentages of cells with the NK phenotype (HNK-1+) were found to be normal, although the majority of patients exhibited decreased numbers of LGL (P less than 0.005). The absolute and relative frequencies of LGL and HNK-1+ lymphocytes by no means correlated with the parasite load. In vitro results suggest an at least partly prostaglandin-mediated and interferon-resistant functional defect of NK cells.

Relationship between intensity of infection and immunomodulation in human schistosomiasis. II. NK cell activity and in vitro lymphocyte proliferation.

Natural killer (NK) cell activity against K-562 targets and lymphoproliferative responses to Con A, interleukin-2 (IL-2) and Con A + IL-2 were examined in a group of 41 Sudanese children suffering from schistosomiasis mansoni and haematobium. The results were correlated to the intensity of infection as determined by enumeration of parasite ova in urine and stool. NK cell activity measured at three effector to target cell ratios was significantly depressed in the patient group as compared to a German control group. Impairment of NK cell activity showed a direct relationship with the patients' parasite load. Furthermore lymphoproliferation to Con A, IL-2 and Con A + IL-2 was depressed in the group of patients. Interestingly the costimulation effect of IL-2 expressed as coefficient of delta ct/min(Con A + IL-2)/delta ct/minCon A correlated significantly to the intensity of infection suggesting that lymphocytes from heavily infected patients were defective in producing appropriate amounts of IL-2 in response to Con A. Our findings support the concept that heavy infections with S. mansoni and/or S. haematobium induce a peculiar dichotomy of cellular and humoral immune parameters. Whereas T cell-dependent cellular immune responsiveness and NK cell function decrease with increasing worm burden specific IgE and IgG antibody responses increase.

Relationship between intensity of infection and immunomodulation in human schistosomiasis. I. Lymphocyte subpopulations and specific antibody responses.

Cellular and humoral immune responsiveness in 44 Sudanese children with schistosomiasis was studied and related to the intensity of infection. The parasite load was quantitated by accurate assessment of the excretion of ova of S. mansoni and S. haematobium in stool and urine, respectively. Lymphocyte subpopulations (T3+, T4+, T8+, TAC+, HNK1+, Ia+, SIg+, LGL+, ANAE+) as well as specific IgE and IgG antibodies to adult schistosome antigens were determined. The relationships existing between intensity of infection and cellular and humoral immune responsiveness revealed a distinct pattern of anti-parasite immunity: The percentage of pan-T cells (T3+) and the T helper (T4+):T suppressor (T8+) ratio were inversely correlated to the intensity of infection. In contrast, the percentage of T suppressor cells positively correlated to the parasite load. Ia+, TAC+, HNK1+ and T4+ cell counts did not show a significant relationship to worm burden. Specific IgE and IgG antibodies to S. mansoni and S. haematobium adult worm antigen clearly increased with the parasite load. The dichotomy of decreased T cell parameters and increased antibody response in heavily infected individuals represents a unique feature in helminthic infections.

The lungfish Protopterus annectans (Owen) as a biocontrol agent against schistosome vector snails.

Laboratory and small-scale field experiments have been carried out to study the malacophagous capabilities of the lungfish Protopterus annectans. When individual fish were offered a range of aquatic fauna in aquaria in the laboratory only snails and dragonfly larvae were consumed. When offered a choice, the fish appeared to prefer snails, with larger individuals (up to 300 mm) capable of consuming up to 200 snails per day. The introduction of five P. annectans into a small concrete pond (diameter 5 m) with an established fauna and flora resulted in a reduction in the snail population of over 90% within 2 weeks. This reduction was maintained over a 4-month observation period suggesting that in habitats in which the lungfish can survive, there is a possibility of significant snail control.

Focality and seasonality of Schistosoma mansoni transmission in the Gezira Irrigated Area, Sudan.

In the Gezira Irrigated Area of Central Sudan, transmission of Schistosoma mansoni was shown to be geographically focal, being concentrated near villages and small settlements. In a study during 1981 and 1982 of the entire area around a typical Gezira village almost 90% of the Biomphalaria pfeifferi snails carrying schistosome infections were found in one minor canal near the village. Sites near smaller settlements some distance from the minor canals yielded few infected snails. The factors which influenced the prevalence of infection in the snails were temperature, turbidity and human contact with the snail habitat. A strategy was proposed for control of Schistosoma transmission through focal and seasonal mollusciciding, health education, chemotherapy, improved water supply and latrine distribution.

Transmission of Schistosoma haematobium in North Gezira, Sudan.

During this 14-month study, 128 765 Bulinus truncatus snails were collected from canals located near four villages in the northern part of the Gezira Irrigated Area, and were examined for patent trematode infections, by exposure to light. In all, 903 shedded cercariae, of which 424 were identified as S. haematobium, and one village, Bashagra, was the source of 80% of these S. haematobium infections. The highest density of snails occurred from March to May and the peak of snail infections occurred from June through August. The residents of the four villages and any adjacent small camps were examined for infection with S. mansoni and/or S. haematobium by collecting and examining stool and urine samples. The overall prevalences were 50% for S. mansoni and 20% for S. haematobium. The age prevalence curves were very different, with the prevalence of S. haematobium falling off more sharply in the over-20 age groups than was the case with S. mansoni. Observations at the human water contact sites suggested that the transmission of S. haematobium was increased when the canals contained shallow stagnant water, when the temperature was above 26 degrees C, and when the site was frequented by small children (particularly boys aged 5-15), for swimming. Our data suggest that at any site the transmission period is short and seasonal.

Snails and aquatic vegetation in Gezira irrigation canals.

All 38 minor canals in a limited area of the Gezira Irrigated Area were surveyed four times over a 2-year period to determine the aquatic and semi-aquatic vegetation types found and their distribution. A more detailed 2-year study of the correlation between snail density and aquatic vegetation was carried out in 18 of these canals. A total of 22 different species of weed were recorded, with floating and submerged weeds being more widespread and dense in the clear, slow-moving water at the end of the irrigation season in March/April, than in the turbid flood waters in October. The schistosome vector snails Biomphalaria pfeifferi and Bulinus truncatus were found in conjunction with aquatic weeds and B. pfeifferi in particular increased in numbers as weed growth continued. In the second season of the study when mechanical weed clearing and regular focal mollusciciding was being carried out there was a noticeable reduction in weed density but repopulation was rapid. Snail numbers were reduced by mollusciciding and/or weed clearance in four canals, but outside the focal target canal stretches the weed clearance alone did not substantially reduce the snail populations.

Dose-finding trial using Oltipraz to treat schoolchildren infected with Schistosoma mansoni in Gezira, Sudan.

A field trial has been carried out in Sudan to determine the optimum dosage regimen for the use of Oltipraz in the treatment of Schistosoma mansoni in schoolchildren. A total of 294 children were treated in six groups to test 15 mg/kg, 20 mg/kg, and 25 mg/kg, using a single oral dose and a divided dose taken some 6 h apart. The children were interviewed before and then 24 h after treatment to determine the prevalence of drug-induced side-effects. Most of the children having complained of abdominal pain before treatment, insisted that they suffered further abdominal pain as a result of the drug. Four children complained of fingertip pain and 17 of blurred vision. The latter side-effect had not previously been recorded in Sudan and, with the fingertip pain, is a cause for concern. There was no difference in the cumulative failure rates between the single and the divided doses, but there was a significant improvement in the efficacy from the 15 mg/kg to the higher doses. The cumulative failure rate increased with higher pretreatment egg count. However at each level the reduction in egg count among failures at the 5-week follow-up, was significant at the 95% probability level. The efficacy of the drug was satisfactory when used at 20 or 25 mg/kg, but the strange side-effects need to be explained before any further use can be recommended.

Treatment with praziquantel of schoolchildren with concurrent Schistosoma mansoni and S. haematobium infections in Gezira, Sudan.

A field trial was conducted in Sudan to evaluate the acceptability and efficacy of praziquantel given to schoolchildren aged 7-11 years who were all infected with both Schistosoma mansoni and S. haematobium. Two dosage regimes were compared, a single dose of 40 mg/kg bodyweight, and a divided dose 2 X 20 mg/kg given 4-6 h apart. When interviewed 24 h after treatment, 80% of the children complained of drug-induced abdominal pain, diarrhoea, nausea or vomiting. However none of the side-effects persisted beyond the day of treatment. More children complained of side-effects from the divided dose than from the single dose. The cure rate in the divided-dose group was slightly better than in the single-dose group but the differences were not significant at any follow-up, nor when results were expressed in terms of cumulative failures. The initial cure rates were 66.3% and 61.8% at 1 month, and 73.2% and 64.7% at 3 months for the divided and single doses respectively. After 12 months there had apparently been considerable reinfection with S. mansoni and 73% of the children were passing eggs. Reinfection with S. haematobium was negligible.

Field trials with Oltipraz against Schistosoma mansoni in the Gezira Irrigated Area, Sudan.

Oltipraz, a new antischistosomal drug, has been field tested in Sudan for acceptability, tolerance and efficacy against Schistosoma mansoni. One hundred and fifty-one school children aged 7 to 12 years were selected for treatment with 20 mg/kg Oltipraz, 78 with a single dose and 73 with a split dose, on the same day. The drug was well tolerated except that 20 children in one school complained of fingertip pain. Parasitological follow-up after 5 weeks, 3 and 6 months produced cure rates (i.e., 2 negative stools) of 41 to 72% with the single dose and 53 to 75% with the split dose. The overall egg output reduction was over 95% from a pretreatment geometric mean egg count of 840 eggs/g. These results indicate that a 20-mg/kg dose of Oltipraz can effectively reduce egg counts but that a larger dose will be required to produce higher cure rates.

Numerical and functional alterations of lymphocytes in human schistosomiasis.

Peripheral blood mononuclear cells from 29 Sudanese children heavily infected with Schistosoma haematobium and S. mansoni were examined for lymphocyte subpopulations, for mitogen responsiveness in the absence and presence of interleukin-2 (IL-2), and for natural killer (NK) cell activity. The nutritional status was assessed by anthropometric and biochemical measurements. In comparison with a group of healthy Caucasian individuals the children with schistosomiasis showed a profound alteration of their cellular immune variables, reflecting a severe acquired immunodeficiency syndrome. The T-cell compartment, in particular the OKT4+ helper/inducer subset, was numerically reduced at the expense of an increased B-cell compartment. The patients' OKT4/OKT8 ratios were significantly diminished (median, 1.2; 95% confidence limits, 0.8-1.7) corresponding to a decreased responsiveness to the T-cell mitogen concanavalin A. Since addition of exogeneous IL-2 significantly enhanced the patients' lymphocyte proliferation in response to Con A, a defective IL-2 production was assumed to be at the origin of the impaired mitogenic response in chronic schistosomiasis. With regard to NK cell activity, most patients' lymphocytes failed to mediate significant cytotoxicity against the K562 target cell line, although normal percentages of cells with the NK phenotype (HNK-1+) were present. The results are discussed in view of immunological alterations seen in other parasitic infections with a heavy parasitic load.