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.

Hepatosplenic morbidity due to Schistosoma mansoni in schoolchildren on Ukerewe Island, Tanzania.

The study was conducted to assess infection intensity and morbidity due to Schistosoma mansoni in schoolchildren on Ukerewe Island in Lake Victoria, Tanzania, East Africa. Three hundred and sixty pupils who have never been treated previously were enrolled (180 males/180 females, age 6-17 years [median 10 years]) in three different schools of the island. Double stool samples were collected from each pupil and egg excretion was classified according to WHO recommendations. Ultrasound investigations were performed in accordance with the WHO Niamey-Belo-Horizonte protocol. Male (112/180, 62.2%) and female (104/180; 57.7%) pupils were infected (difference, not significant [n.s.]). In the positive 216 cases, egg excretion varied from 1 to 2,440 eggs per gramme stool (epg) [median 165 epg]. There were 69/216 (31.9%) who had a low grade, 105/216 (53.2%) had a moderate and 42/216 (14.8%) had a heavy infection. There was no significant difference between male and female sex nor with regard to age groups. There were 354/360 children who underwent sonography: 321 (90.7%) had splenomegaly, 316 (89.3%) showed a left lobe and 109 (30.9%) had a right lobe hepatomegaly. Overt signs of portal fibrosis (PF) were present in 19 children (5.4%) out of whom 11 presented with echogenic thickening of peripheral portal and 8 with thickening of central portal branches. Non-specific portal wall changes were seen in 6 children (1.7%). Association of PF to quantitative egg excretion was not seen (median in PF, 172 epg vs. median in non PF, 168 epg; difference, n.s.). Portal vein dilatation was seen in 101/354 (28.5%) cases. In Ukerewe, the prevalence of S. mansoni infection and infection intensity in children is high, yet overt hepatic morbidity is low as compared to other endemic foci. Non-specific ultrasonographic abnormalities including hepatosplenomegaly and portal vein dilatation were seen frequently but the fraction attributable to schistosomiasis is difficult to assess.

Patterns of malaria related mortality based on verbal autopsy in Muleba District, north-western Tanzania.

Reliable malaria related mortality data is important for planning appropriate interventions. However, there is scarce information on the pattern of malaria related mortality in epidemic prone districts of Tanzania. This study was carried out to determine malaria related mortality and establish its trend change over time in both epidemic and non-epidemic areas of Muleba District of north-western Tanzania. A verbal autopsy survey was conducted to obtain data on all deaths of individuals who died in six randomly selected villages from 1997 to 2006. Relatives of the deceased were interviewed using a standardized questionnaire. Communicable diseases accounted for about two thirds (61.9%) of deaths among > or =5 years individuals and 84.8% in < or =5 years. Non-communicable diseases accounted for 28.9% and 14.1% deaths in > or =5 years and < or =5 years, respectively. Malaria was the leading cause of deaths in all age groups (40.3%) and among children <5 years (73.8%). Infants accounted for about two third (64.5%) of all malaria related deaths in children <5 years. Peak of malaria proportional mortality was highest during malaria epidemics. Most of the malaria-related deaths in this group were among 1-12 months (64.5%) followed by 13-24 months (20.9%), and 25-59 months (14.8%). Cerebral malaria accounted for 18.9% (N=32) of death related to malaria in all age groups; 12.1% (17/141) were in under-five, 42.9% (6/14) were in 5-14 years and 64.3% (9/14) in 15-70 years old. More than half of malaria related deaths (61.0%) in <5 years children were associated with severe anaemia followed by diarrhoeal disease (24.1%), cerebral malaria (12.5%) and respiratory infection (8.5%) as common conditions. The majority of the deceased caretakers first sought treatment at health facilities within 24hr of the onset of illness. Significantly a higher proportion of caretakers of the underfives in the epidemic area sought treatment within 24hr than in non-epidemic area (39.3% vs. 18.5%; P = 0.0385). In conclusion, malaria accounts for majority of deaths in Muleba district, with substantial proportion being attributed to malaria epidemics.

Antimicrobial susceptibility of Shigella flexneri and S. dysenteriae isolated from stool specimens of patients with bloody diarrhoea in Mwanza, Tanzania.

This study was conducted to determine frequency and pattern of antimicrobial susceptibility of Shigella species isolated from stool specimens collected from patients presenting with bloody diarrhoea in Mwanza City, Tanzania. The study was carried out from October 2004 to October 2005 and involved patients attending Sekou Toure Regional Hospital and Butimba Health Centre. Bacteriological cultures were done at the National Institute for Medical Research laboratory. A total of 489 patients (median age = 20 years) participated in the study and were able to provide stool specimens. Shigella species were isolated from 14% (69/489) of the stool specimens collected. Of the sixty nine strains of Shigella spp isolated, 62 (90%) were S. flexneri and 7 (10%) were S. dysenteriae. All Shigella strains isolated showed high resistance to ampicillin, tetracycline, trimethoprim-sulphamethoxazole and chloramphenicol, drugs commonly used for management of shigellosis in Tanzania. However all isolates were fully susceptible to ciprofloxacin, nalidixic acid, erythromycin, cefuroxime and gentamycin. S. flexneri showed resistance to amoxy-clavulanic_acid and azithromycin in 5% and 2% of isolates, respectively. None of the S. dysenteriae isolates were resistant to these two drugs. Entamoeba histolytica, Giardia lamblia and Schistosoma mansoni were microscopically detected in 16.5%, 4.4% and 5.3% of patients, respectively. These findings suggest that there is a need to carry out extensive susceptibility studies in different parts of the country with view of re-appraising the current guidelines for management of bloody diarrhoea in Tanzania.

Caretaker's perceptions, attitudes and practices regarding childhood febrile illness and diarrhoeal diseases among riparian communities of Lake Victoria, Tanzania.

Understanding community perceptions and attitudes towards childhood illness is important in developing appropriate interventions. A cross sectional survey was therefore, conducted in a riparian community of Lake Victoria basin in Tanzania to determine caretakers' perception, attitudes and practices on childhood malaria and diarrhoeal diseases. Among 336 caretakers interviewed, 61.1% (205) reported febrile illness in children within three months and 26.0% reported a diarrhoeal episode among children within two weeks before the survey. The majority of the respondents reported high fever (98.7%) and prostration (53.7%) as major symptoms of severe malaria. Convulsions were associated with high fever by only 13.7% of the respondents. Forty percent of the respondents attributed convulsions in children to either fever or malaria, and 24.4% correctly mentioned high fever or malaria. A health facility was the first point of care for childhood malaria for the majority (73%) of the respondents. In diarrhoeal diseases, prostration-weakness (67.7%) and dysentery (20.4%) were commonly reported among the respondents. Typical symptoms of severe dehydration (sunken eyes, loss of skin turgor, dry tears) were poorly recognised as characteristics of severe diarrhoeal diseases. Over 85% of the respondents practiced appropriate dietary measures or increased fluid intake for a child who had diarrhoea. Use of anti-diarrhoea (40.8%) and antibiotic medications (34.8%) were common in the treatment of diarrhoeal diseases. It is important that health education emphasizing recognitions of danger signs/symptoms of malaria and diarrhoeal diseases and their management is strengthened among riparian communities in Lake Victoria basin.

Validation of a WHO algorithm with risk assessment for the clinical management of vaginal discharge in Mwanza, Tanzania.

OBJECTIVES: (i) To determine the microbial aetiologies of vaginal discharge in STD clinic and antenatal clinic (ANC) attenders; (ii) to evaluate the performance and costs of a new WHO algorithm for the detection of gonococcal and chlamydial infections in women complaining of vaginal discharge and/or genital itching, using a risk assessment. METHODS: Two groups were enrolled: (i) 395 consecutive female patients attending a hospital outpatient clinic complaining of genital discharge or itching; and (ii) 628 consecutive pregnant women reporting at an urban ANC these symptoms. Patients were interviewed by a nurse, who applied the WHO risk score. They were then referred to the study room for interview concerning the same and other risk factors, examined, and sampled for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), and Candida albicans (CA). Sensitivity, specificity, positive predictive value, overtreatment and correct treatment rates, and cost of drugs per true case treated were estimated. RESULTS: The prevalence of NG and/or CT infections was 11.4% and 8% at the STD clinic and the ANC respectively. The most prevalent pathogens were CA (38% at both clinics) and TV (25% at the STD clinic and 34% at the ANC). The sensitivity of the WHO algorithm for NG and/or CT was 62% at the STD clinic and 46% at the ANC, and the specificities were 64% and 84% respectively. The operational feasibility of the method was good. The cost of drugs per true case treated in applying the risk assessment approach was $3.5 among nonpregnant women and $5.0 among pregnant women. This compared favourably with respective costs of $8.8 and $25.0 in applying the syndromic management alone. CONCLUSIONS: The WHO risk assessment algorithm for the diagnosis of NG and/or CT infections among women complaining of genital discharge can considerably reduce overtreatment of NG and/or CT in both pregnant and non-pregnant women, but in this study it failed to identify 38% of non-pregnant and 54% of pregnant women with these infections. The elements of the risk score may need adjustment in different settings.

STD rapid assessment in Rwandan refugee camps in Tanzania.

OBJECTIVE: To obtain baseline information on sexually transmitted diseases (STDs) in the Rwandan refugees camps in Tanzania, prior to establishment of STD services. SETTING: The largest camps of Rwandan refugees in the Ngara District of Tanzania (estimated population 300,000). The study was carried out in 8 days in August 1994. SUBJECTS AND METHODS: A rapid assessment technique was used to measure STD prevalences among: (i) 100 antenatal clinic attenders (ANC); (ii) 239 men from outpatient clinics (OPD); and (iii) 289 men from the community. Interviews (by questionnaire) and genital examination were performed for all participants; sampling for females included genital swabs for the the diagnosis of Neisseria gonorrhoeae (NG), Candida albicans (CA), Trichomonas vaginalis (TV), bacterial vaginosis (BV) and a blood sample for syphilis serology. Men provided urine samples which were screened for leucocytes using the leucocyte esterase (LE) dipstick; urethral swabs for Gram stain were taken from men with a reactive LE test and from those with symptoms or signs of urethritis. OPD males provided a blood sample for syphilis serology. RESULTS: All groups reported frequent experience with STDs and engaging in risky sexual behaviour prior to the survey. During the establishment of the camps, sexual activity was reportedly low. Over 50% of ANC attenders were infected with agents causing vaginitis (TV/BV/CA) and 3% were infected with NG. The prevalence of active syphilis was 4%. In the male outpatients, the prevalence of urethritis was 2.6% and of serological syphilis was 6.1%. Among males in the community, the prevalence of urethritis was 2.9% (the majority being asymptomatic infections). We noted frequent over-reporting of STD symptoms, unconfirmed clinically or biologically. CONCLUSIONS: STD case detection and management should be improved by training health workers in using the WHO syndromic approach, and through IEC campaigns encouraging attendance at clinics. Rapid epidemiological methods provide quick and useful information at low cost in refugee camps.