Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

BACKGROUND: The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. METHODS: Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. RESULTS: The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. CONCLUSION: The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Integrated community case management and community-based health planning and services: a cross sectional study on the effectiveness of the national implementation for the treatment of malaria, diarrhoea and pneumonia.

BACKGROUND: Ghana has developed two main community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and pneumonia: the Home-based Care (HBC) and the Community-based Health Planning and Services (CHPS). The objective was to assess the effectiveness of HBC and CHPS on utilization, appropriate treatment given and users' satisfaction for the treatment of malaria, diarrhoea and pneumonia. METHODS: A household survey was conducted 2 and 8 years after implementation of HBC in the Volta and Northern Regions of Ghana, respectively. The study population was carers of children under-five who had fever, diarrhoea and/or cough in the last 2 weeks prior to the interview. HBC and CHPS utilization were assessed based on treatment-seeking behaviour when the child was sick. Appropriate treatment was based on adherence to national guidelines and satisfaction was based on the perceptions of the carers after the treatment-seeking visit. RESULTS: HBC utilization was 17.3 and 1.0 % in the Volta and Northern Regions respectively, while CHPS utilization in the same regions was 11.8 and 31.3 %, with large variation among districts. Regarding appropriate treatment of uncomplicated malaria, 36.7 % (n = 17) and 19.4 % (n = 1) of malaria cases were treated with ACT under the HBC in the Volta and Northern Regions respectively, and 14.7 % (n = 7) and 7.4 % (n = 26) under the CHPS in the Volta and Northern Regions. Regarding diarrhoea, 7.6 % (n = 4) of the children diagnosed with diarrhoea received oral rehydration salts (ORS) or were referred under the HBC in the Volta Region and 22.1 % (n = 6) and 5.6 % (n = 8) under the CHPS in the Volta and Northern Regions. Regarding suspected pneumonia, CHPS in the Northern Region gave the most appropriate treatment with 33.0 % (n = 4) of suspected cases receiving amoxicillin. Users of CHPS in the Volta Region were the most satisfied (97.7 % were satisfied or very satisfied) when compared with those of the HBC and of the Northern Region. CONCLUSIONS: HBC showed greater utilization by children under-five years of age in the Volta Region while CHPS was more utilized in the Northern Region. Utilization of HBC contributed to prompt treatment of fever in the Volta Region. Appropriate treatment for the three diseases was low in the HBC and CHPS, in both regions. Users were generally satisfied with the CHPS and HBC services.

Vitamin D3supplementation and childhood diarrhea: a randomized controlled trial.

OBJECTIVE: To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan. METHODS: This double-blind placebo-controlled trial randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 (cholecalciferol 100000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≥ 3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models. RESULTS: No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per child-year (95% CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons. CONCLUSIONS: Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases.

Evaluation of gravid traps for the collection of Culex quinquefasciatus, a vector of lymphatic filariasis in Tanzania.

BACKGROUND: Although several studies have suggested that gravid traps might be useful for collection of mosquitoes, particularly Culex quinquefasciatus, to monitor transmission of the nematode Wuchereria bancrofti (xenomonitoring), there has not been a study to see which of the currently available gravid traps is most effective in endemic areas. The present study evaluated the comparative efficacy for collection of Cx quinquefasciatus of four commercially available gravid traps: the CDC, Frommer Updraft, Reiter-Cummings and Harris County traps. METHOD: Trap evaluations were conducted in two locations in Tanzania, Ifakara and Tanga. Mosquitoes collected were identified to species, sex, and gonotrophic status. RESULTS: In both locations, the CDC gravid trap collected the highest number of mosquitoes, the highest number of Cx quinquefasciatus, and the highest proportion of gravid mosquitoes. Although it damaged the highest proportion of mosquitoes as they passed through the trap fan, the CDC gravid trap also contained the highest number of living mosquitoes, when the traps were collected in the morning. The CDC gravid traps collected significantly more phlebotomine sandflies than the other traps and in Tanga, where they were more frequent, the highest number of biting midges. CONCLUSION: The effectiveness of all four gravid traps should encourage the sampling of Cx quinquefasciatus where it is an important disease vector or nuisance mosquito. The unexpected collection of phlebotomine sandflies and biting midges indicates that gravid traps might usefully collect other insects, including those of medical importance.

Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial.

BACKGROUND: Vitamin D has a role in regulating immune function, and its deficiency is a suggested risk factor for childhood pneumonia. Our aim was to assess whether oral supplementation of vitamin D(3) (cholecalciferol) will reduce the incidence and severity of pneumonia in a high-risk infant population. METHODS: We did a randomised placebo-controlled trial to compare oral 100,000 IU (2·5 mg) vitamin D(3) with placebo given to children aged 1-11 months in Kabul, Afghanistan. Randomisation was by use of a computer-generated list. Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months. Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically. Our primary outcome was the first or only episode of radiologically confirmed pneumonia. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00548379. FINDINGS: 1524 children were assigned to receive vitamin D(3) and 1522 placebo. There was no significant difference between the incidence of first or only pneumonia between the vitamin D (0·145 per child per year, 95% CI 0·129-0·164) and the placebo group (0.137, 0·121-0·155); the incidence rate ratio was 1·06 (95% CI 0·89-1·27). From 652 children during five separate periods of testing serum calcifediol, only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group--a toxic level. INTERPRETATIONS: Quarterly bolus doses of oral vitamin D(3) supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting. FUNDING: Wellcome Trust and British Council.

Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial.

OBJECTIVES: To determine whether (i) supplementation of oral 100,000 iu of vitamin D(3) (cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii) supplementation will reduce the risk of repeat episodes. METHODS: Double-blind individually randomised placebo-controlled trial in an inner-city hospital in Kabul, of 453 children aged 1-36 months, diagnosed with non-severe or severe pneumonia at the outpatient clinic. Children with rickets, other concurrent severe diseases, very severe pneumonia or wheeze, were excluded. Children were given vitamin D(3) or placebo drops additional to routine pneumonia treatment. RESULTS: Two hundred and twenty-four children received vitamin D(3;) and 229 received placebo. There was no significant difference in the mean number of days to recovery between the vitamin D(3) (4.74 days; SD 2.22) and placebo arms (4.98 days; SD 2.89; P = 0.17). The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention (92/204; 45%) than the placebo group [122/211; (58%; relative risk 0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the vitamin D(3) group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53-0.95; P = 0.02). CONCLUSION: A single high-dose oral vitamin D(3) supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia.