5-Nitroimidazole refractory giardiasis is common in Matanzas, Cuba and effectively treated by secnidazole plus high-dose mebendazole or quinacrine: a prospective observational cohort study.

OBJECTIVE: To evaluate the effectiveness and tolerability of secnidazole combined with high-dose mebendazole for treatment of 5-nitroimidazole-resistant giardiasis. METHOD: Adults with microscopically verified Giardia intestinalis monoinfection attending a secondary level hospital in Matanzas City, Cuba were prospectively included in a cohort. A recently introduced treatment ladder consisting of metronidazole as first-line treatment, followed by secnidazole, tinidazole, secnidazole plus mebendazole and quinacrine as second-to fifth-line treatments, respectively, was used. Adverse events and treatment success were determined by questioning and microscopy on concentrated stool samples, respectively on days 3, 5 and 7 after the end of treatment. If G. intestinalis was detected on day 3, 5 or 7, then the infection was classified as refractory and no further microscopy was performed. RESULTS: A total of 456 individuals were included. Metronidazole, 500 mg three times daily for 5 days, cured 248/456 (54%) patients. A single 2-g secnidazole dose as second-line treatment cured 50/208 (24%) patients. A single 2-g tinidazole dose as third-line treatment cured 43/158 (27%) patients. Three rounds of 5-nitroimidazole therapy therefore cured 341/456 (75%) patients. Secnidazole plus mebendazole (200 mg every 8 hours for 3 days) cured 100/115 (87%) of nitroimidazole refractory infections. Quinacrine cured the remaining 15 patients. All treatments were well tolerated. CONCLUSIONS: 5-Nitroimidazole refractory giardiasis was common, indicating that an alternative first-line treatment may be needed. Retreatment of metronidazole refractory giardiasis with an alternative 5-nitroimidazole was suboptimal, indicating cross-resistance. Mebendazole plus secnidazole were well tolerated and effective for the treatment of 5-nitroimidazole refractory G. intestinalis infection in this setting.

Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial.

BACKGROUND: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. METHODS: The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency or no Danish-speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. RESULTS: Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). CONCLUSION: Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76).

Bacillus Calmette-Guérin vaccination at birth and in vitro cytokine responses to non-specific stimulation. A randomized clinical trial.

Several studies have shown increased in vitro cytokine responses to non-related pathogens after Bacillus Calmette-Guérin (BCG) vaccination. A total of 158 infants (80 BCG administered within 7 days of birth; 78 controls) were bled 4 days post-randomization, and at age 3 and 13 months. Geometric mean concentrations of IL-1ß, TNF-α, IL-6 (24 h stimulation) and IFN-γ, IL-10, IL-17, IL-22 (96 h stimulation) in response to in vitro stimulation with RPMI, LPS, PHA, Escherichia coli, Streptococcus pneumoniae, Candida albicans and BCG were compared among BCG vaccinated children and controls. BCG vaccination did not affect in vitro cytokine production, except IFN-γ and IL-22 response to BCG. Stratifying for 'age at randomization' we found a potentiating effect of BCG on cytokine production (TNF-α, IL-6, IL-10) in the 4 days post randomization stimulations, among children who were vaccinated at age 2-7 days versus age 0-1 days. BCG vaccination did not potentiate cytokine production to non-BCG antigens. At 4 days post randomization, BCG was associated with higher cytokine production in the later randomized children.

An unplanned delay between control visits influences the metabolic status in children with diabetes: an observational study.

AIM: To evaluate whether the metabolic status had been influenced by the longer interval between visits because of a strike at the diabetes outpatient clinic. METHODS: During the strike from April 16 to June 15, 2008 all routine visits were cancelled. The HbA1c values from the last two visits prior to and the first two visits after the strike were compared with the values from the same periods the previous year. Danish speaking patients answered a questionnaire. RESULTS: For 155 children included, the mean HbA1c values before the strike were 8.1 and 8.1 (p = 0.39), while the value increased to 8.5 at the first visit (p < 0.0001) and 8.4 at the second visit following the strike (p = 0.14). No differences were found between any of the HbA1c values measured in 2007 (p > 0.05). Of the 152 questionnaires handed out, 113 (74.3%) were returned. Of these, 48 (42.5%) stated to have needed help, and 49 (43.3%) that their children's diabetes had deteriorated because of the strike. CONCLUSIONS: In this unplanned study, the increase of 0.4% in mean HbA1c supports previous findings that the interval between visits at a diabetic clinic is important for ensuring an acceptable metabolic control in children with diabetes.

A household study of chickenpox in Guinea-Bissau: intensity of exposure is a determinant of severity.

OBJECTIVE: To determinate the relative importance of state of nutrition and intensity of exposure for clinical severity of chickenpox in a developing country. METHODS: A prospective household study was performed in a semi-urban area in Bissau, the capital of Guinea-Bissau, between December 1994 and June 1995. Antibodies were measured in the acute and the convalescence phase to assess validity of clinical diagnoses. The clinical severity of infection was assessed by number of pox, fever response and skin infections. Severity was compared for index cases, i.e. the first case in the house, and secondary and tertiary cases infected following exposure at home. RESULT: Chickenpox was diagnosed in 165 persons. The clinician's and the mothers' diagnoses corresponded well with the serological results. Median age was 36 months (range 3 months to 30.3 years). There was no correlation between nutritional status measured by arm-circumference and severity of infection. The number of pox was higher for secondary cases than for index cases (median 106 vs. 89, P<0.01), the difference being more pronounced for girls (P=0.018) than for boys (P=0.575). The risk of skin infection as a complication was correlated with the number of pox (P<0.001). CONCLUSION: Chickenpox was recognised correctly by Guinean mothers. The age distribution in Guinea-Bissau resembled the pattern in developed countries. The intensity of exposure was a major determinant of severity, especially for girls.

Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country.

OBJECTIVE: To compare detection of respiratory syncytial virus (RSV) for diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in different clinical settings in a community study in Guinea-Bissau. METHOD: During 1996-98 paired specimens were obtained from 635 children under 5 years of age (median: 274 days; interquartile range: 144-453 days) with symptoms of lower respiratory infections (LRI). The specimens were analysed by an enzyme-linked immunosorbent assay for RSV antigen in Guinea-Bissau and re-analysed in Denmark using the same assay. The gold standard for RSV antigen detection was defined as any test being positive. RESULTS: RSV antigen was detected in 84 (13%) children, the prevalence being 19% (41/219) among infants aged < 6 months, 12% (22/184) in infants aged 6-11 months, and 9% (21/230) in older children. Sensitivity of antigen detection was higher in NPA (92% in analyses in Guinea-Bissau and 98% in Denmark) than in NS (63% in analyses in Guinea-Bissau, 71% in Denmark). Specificity of RSV antigen detection was equally high in NPA and NS (99-100%). Time since onset of symptoms was significantly shorter in RSV antigen positive than negative samples. Sensitivity did not depend on clinical setting or age of the child. CONCLUSION: Using NS samples was associated with a 27-31% reduction in sensitivity compared with NPA specimens. As NPAs are costly and considered a nuisance by the population, it might be cost-effective in larger epidemiological studies to lose 25-30% in sensitivity but be able to collect samples from a much larger population.

Duration of secretory IgM and IgA antibodies to respiratory syncytial virus in a community study in Guinea-Bissau.

Respiratory syncytial virus (RSV) is probably the single major cause of lower respiratory infection (LRI) among infants worldwide. Its relative importance may be underestimated, as the diagnosis is based on antigen detection and antigen may only be detectable in the early phase of infection. We have therefore assessed the duration of secretory IgM and IgA antibody responses and whether assays for these antibodies can be used to improve the diagnosing of RSV-associated infections. During two RSV epidemics in Guinea-Bissau, 32 RSV antigen-positive children with LRI were followed with sequential nasopharyngeal suction on days 7, 14, 30, 60 and 120 in the first epidemic and every fortnight for 6 mo after the second epidemic to measure the duration of secretory IgM and IgA responses. Nearly all of the children had an IgM response during the first month after infection. The response ratio was highest on days 7 and 14, being 84% and 71%, respectively. After 30 d the IgM response decreased rapidly. Among 27 age- and sex-matched controls, only 1 child was positive for IgM. During the second epidemic, when the children were followed more intensively, half of the children were IgM-positive after the acute phase of infection. A secondary response may be more likely in children with low IgM responses in the acute phase (RR = 2.08 (95% confidence interval (CI) 0.92-4.70)). The IgA response was highest on days 28 and 42 after antigen detection, 72% having a detectable IgA response within the first 1.5 mo. Among 27 controls, only 2 were IgA-positive (7%). In the second epidemic with more intensive follow-up, 62% (8/13) of the IgA-positive children had a response that lasted 10 wk. Of the children with no persistent IgA response, half (5/10) had a subsequent IgA-positive response after the first 42 d. All of these children had a simultaneous IgM-positive response. When 29 of the children were tested after an epidemic when they were 1-3-y-old, >80% again had high IgM (24/29, 82%) and IgA (28/29, 94%) levels. Among samples collected over a 1-y period from infants with LRI in a community morbidity surveillance conducted at the local health centre and via paediatric outpatient consultation, 17% (110/659) were antigen-positive, 26% (171/659) IgM-positive and 38% (248/659) either antigen- or IgM-positive. IgM responses are short-lived among infants and may therefore be used as an indication of recent RSV infection among children with LRI. Using both antigen and IgM detection may significantly improve our detection of RSV infections.

Low-dose quinine for treatment of Plasmodium falciparum malaria in Guinea-Bissau.

The recommended dose of 10 mg quinine/kg bodyweight 3 times a day for 7 days for treatment of malaria is so high that many patients experience cinchonism. We have earlier obtained good results with 7 days' treatment with 20 mg Quinimax/kg bodyweight divided into 2 daily doses. In order to identify the lowest effective dose, children with symptomatic malaria were treated with quinine twice a day for 7 days. They were assigned to 1 of 3 groups treated daily with 10 mg/kg, 15 mg/kg, or 20 mg/kg bodyweight, respectively; 42, 46, and 34 children, respectively, received treatment and completed 5 weeks of follow-up. The cumulative percentages of all children with parasitaemia during follow-up on day 28 or before were 33%, 13% and 12%, respectively. Treatment with 10 mg quinine salt/kg daily for 7 days gave a significantly higher rate of recrudescence than did treatment with 15 or 20 mg/kg daily. Thus at least 15 mg of quinine salt/kg bodyweight daily should be recommended for treatment of symptomatic Plasmodium falciparum malaria in Guinea-Bissau.

Secretory IgM and IgA antibodies to respiratory syncytial virus in nasopharyngeal aspirates: a diagnostic supplement to antigen detection.

BACKGROUND: RSV-shedding during an RSV-infection declines dramatically after the first week of infection. It could be of interest to be able to diagnose RSV-infection for a longer period of time by detection of specific RSV-IgM and RSV-IgA in nasopharyngeal aspirates (NPA) in order to minimize unnecessary antibiotics. OBJECTIVES: To evaluate an ELISA to detect specific RSV-IgM and RSV-IgA in NPA as a supplement to RSV-antigen detection. STUDY DESIGN: A total of 104 NPA from 101 children (median age 9 months) with acute respiratory disease (group 1) admitted to hospital and consecutive NPA (collected on day 0, 7, 14, 30 and 60) from 11 children (median age 3 months) with a proven RSV infection (group 2) were collected. All NPA from group 1 were analysed for RSV-antigen, RSV-IgM and RSV-IgA. NPA from group 2 were analysed for RSV-IgM and RSV-IgA. RESULTS: Thirty-five NPA in group 1 were positive for RSV-antigen and 64 were positive for RSV-antigen test alone found 44% and the RSV-IgM test alone found 80%. In group 2 8/11 (73%) has an excellent RSV-IgM response day 7, the rest responded later. Only 5/11 (46%) had a less pronounced RSV-IgA response on day 7, three cases responded later and three did not respond at all. RSV-IgM disappeared in 8/11 (73%) and RSV-IgA in 7/8 (88%) between day 30-60. CONCLUSIONS: Specific RSV-IgM is a valuable supplement to RSV-antigen detection for the diagnosis of acute and recent RSV infection.

Comparison of 3, 5 and 7 days' treatment with Quinimax for falciparum malaria in Guinea-Bissau.

For treatment of malaria, the World Health Organization recommends 10 mg of quinine per kg body-weight 3 times a day for at least 7 d. In Guinea-Bissau, as in several other African countries, a 3 d treatment regimen (10 mg/kg twice daily) is currently used. We therefore compared the 3 d treatment period with periods of 5 and 7 d. A total of 145 children with clinical malaria due to monoinfection with Plasmodium falciparum, with > or = 20 parasites per 200 leucocytes, were treated with intramuscular Quinimax 10 mg per kg body-weight twice daily for 3, 5 or 7 d. The children were then examined once weekly for 4 weeks. Following the 3 d treatment regimen, 34 of 43 children (79%) had parasitaemia on day 28 or before; following the 5 d treatment regimen, 36 of 40 children (90%) did so; and following the 7 d treatment regimen, 7 of 62 children (11%) were parasitaemic at that time. This study thus suggests that the currently recommended 3 d Quinimax treatment regimen in Guinea-Bissau for moderate and severe malaria is not effective.

Lifetime of reusable syringes and needles. A field study.

For planning of supplies and costs it is important for an immunization unit to know how many times reusable syringes and needles can be used. A field study found that BCG syringes, which had their rubber seals replaced once, could be used at least 150 times, and DPT syringes more than 200 times even when sterilized in tap water with a hardness of 88 mg calciumoxyde per liter. Needles could be used 100 times and when resharpened several times even more.

Compliance with diphtheria, tetanus, and pertussis immunisation in Bangladesh: factors identifying high risk groups.

OBJECTIVE: To evaluate factors associated with non-compliance with having second vaccination against diphtheria, tetanus, and pertussis in a treatment centre in Dhaka to determine which children were most at risk of not completing immunisation. DESIGN: Cohort study of infants given first dose of the vaccine and followed up six weeks later to ascertain compliance with having second dose. Factors associated with non-compliance were evaluated. SETTING: Dhaka treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 136 unimmunised children aged 6 weeks to 23 months who lived within reach of the treatment centre. At time of the six week follow up 16 of the children could not be traced and seven had died. INTERVENTIONS: All children received their first dose of the vaccine. In each case health education workers had informed the mother about the value of immunisation, and she was given clear instructions to bring the child back after four weeks for the second dose. MAIN OUTCOME MEASURE: Rate of non-compliance with advice to return child for second vaccination. RESULTS: 46 of 113 children (41%) received the second dose of the vaccine. Factors most closely associated with mothers' failure to comply with the second dose were lack of education and low income. Children whose mothers knew most about immunisation at first interview were more likely to have their second dose. CONCLUSIONS: Preventive health care services such as immunisation are appropriately offered in treatment centres, but compliance among children varies with socioeconomic status and mother's education. Further research should be aimed at ways to make health education more effective among uneducated parents.

PIP: Factors associated with noncompliance with have a 2nd vaccination against diphtheria, tetanus, and pertussis in a treatment center in Dhaka were evaluated in order to determine which children were most at risk for not completing their immunization. This cohort study of infants was conducted at the Dhaka treatment center of the International Center for Diarrheal Disease Research, Bangladesh and included 136 unimmunized children ages 6 weeks-23 months who lived within reach of the treatment center. 1st doses of the vaccination were given and followed up 6 weeks later to ascertain compliance with having the 2nd dose. At the 6-week followup, 16 of the children could not be traced and 7 had died. All children received their 1st dose of the vaccine. In each case, health education workers had informed the mother about the value of immunization, and she was provided clear instructions concerning the return of the child after 4 weeks had passed for the 2nd dose. Rate of noncompliance with advice to return the child for 2nd vaccination was the main outcome measure. 46 of 113 children (41%) received the 2nd vaccine dose. Factors most closely associated with maternal failure to comply with 2nd dose were lack of education and low income. Children whose mothers know most about immunization at 1st interview were more likely to have their 2nd dose. Preventive health care services such as immunization are appropriately offered in treatment centers but compliance among children varies with socioeconomic status and maternal education. Further research should be aimed at ways to make health education more effective among uneducated parents.

Can mothers safely prepare labon-gur salt-sugar solution after demonstration in a diarrhoeal hospital?

Home-based salt-sugar solution (SSS) prepared with labon (locally produced sea salt) and gur (unrefined brown sugar) has been recommended as a cheap, locally available and a simple tool to prevent and treat diarrhoeal dehydration. Preparation of labon-gur SSS is demonstrated to the patients and the attendants at ICDDR, Bangladesh. To evaluate performances, 150 mothers were asked to measure labon and gur by finger pinch and first method and 100 mothers measured half a seer of water to prepare labon-gur SSS, shortly after the demonstration sessions. 4.0% of the samples exceeded the upper safety limit while 1.3% exceeded the upper danger limit for salt and 98.7% samples of gur were within safe and effective range. Mothers' performances were not different with regard to their educational status and prior practice at home. 80% knew about the solution before coming to the hospital and 45% had utilized this knowledge. Our study suggests that demonstration of home-based SSS in a diarrhoeal hospital may positively affect health education and that health personnel should actively participate in increasing health awareness.

Immunisation in a curative setting.

OBJECTIVE: To study the uptake of vaccination offered to women and children attending a curative health facility. DESIGN: Prospective survey over eight months of the uptake of vaccination offered to unimmunised women and children attending a diarrhoeal treatment centre as patients or attendants. SETTING: The International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. SUBJECTS: An estimated 19,349 unimmunised women aged 15 to 45 and 17,372 children attending the centre for treatment or accompanying patients between 1 January and 31 August 1989. MAIN OUTCOME MEASURES: The number of women and children who were unimmunised or incompletely immunised was calculated and the percentage of this target population accepting vaccination was recorded. RESULTS: 7530 (84.2%) Of 8944 eligible children and 7730 (40.4%) of 19,138 eligible women were vaccinated. Of the children, 63.8% were boys, 75.9% were aged under 1 year, and 23.0% were aged 1 to 2 years. The estimated number of missed opportunities for vaccination was 716 among the children (8.0% of the target population) and 11,408 among the women (59.6% of those eligible). CONCLUSION: It is possible to establish immunisation services at a health facility treating acutely ill patients.

PIP: The objective of this study was to explore the uptake of vaccinations offered to women and children attending a curative health facility. The design was a prospective survey of over 8 months of uptake of vaccinations offered to unimmunized women and children attending a diarrheal treatment center as patients or attendants. The setting of the study was the International Center for Diarrheal Disease Research in Dhaka, Bangladesh. The subjects of the study included an estimated 19,349 unimmunized women aged 15-45 and 17,372 children attending the Center for treatment or accompanying patients between January 1 and August 31, 1989. The number of women and children who were unimmunized or incompletely immunized was calculated and the % of this target population accepting vaccination was recorded. The results were: 7530 (84.2%) of 8944 eligible children and 7730 (40.4%) of 19,138 eligible women were vaccinated. Of the children 66.8% were boys, 75.9% were aged under 1 year and 23.0% were aged 1 and 2 years. The estimated number of missed opportunities for vaccination was 716 among the children (8.0% of the target population) and 11,408 among the women (59.6 of those eligible). The conclusions were that it was possible to establish immunization services at a health facility treating acutely ill patients (Author's modified).

[Testing of a liquid, ready-to-use, breast milk substitute in the county of Funen]. / Afprøvning af flydende, faerdigtilberedt modermaelkserstatning i Fyns Amt.

A newly developed liquid ready-to-use cow's milk based formula (BD) was used as the sole nutrient in 314 healthy term infants below the age of 28 weeks--except for supplementary feeding introduced at an average age of 142 days. The incidence of dyspeptic problems (constipation, diarrhea, vomiting), the parents' and visiting nurses' comments on the product, and the causes of "BD failure" (termination of BD feeding because of suspected cow's milk allergy, dyspepsia, etc.) were recorded as were rates of weight gain and linear growth. It is concluded that BD is a valuable alternative to existing powdered milk formulas and that the growth of the infants compared satisfactorily with published reference values.

[Breast milk substitutes based on cow milk]. / Komaelksbaserede modermaelkserstatninger.

"Adapted" or "humanized" breast-milk substitutes based on cows' milk are manufactured according to directives from a publication issued by the Ministry of Agriculture. The accepted recommendations for the daily intake (RDA) of nutrients is adjusted to the neonates' relatively low tolerance and provides a certain margin of safety in case of illness and slight inaccuracies in preparation. The recommendations are, however, often based on animal experiments, studies of pathological conditions etc. because the needs of the neonate are not known. There is a fundamental difference between RDA for chemical energy and various nutrients as the energy requirement is stated on the basis of average values while the requirements for specific nutrients are gives as upper and lower limiting values. In addition to nutrients, a long series of hormones, enzymes and antimicrobial factors are transferred to the infant via breast-milk. The nutritional significance of these is entirely or partially unknown. It is thus impossible to give the bottle-fed infant a diet which is quantitatively and qualitatively identical with that of a breastfed baby. Nevertheless, experience has shown that bottle-feeding usually proceeds satisfactorily. Galactosaemia and certain forms of medication in the mother constitute absolute contraindications to breast-feeding while phenylketonuria, certain maternal infections are relative contraindications to breast-feeding. Mothers should be prepared for breast-feeding already during pregnancy but in the cases where the mother cannot, should not or does not wish to breast-feed, it is important to counteract any feelings of guilt, neglect or incompetence and, on the other hand, give her thorough training in artificial feeding of the infant.