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Objectives: Studies from low-income countries have suggested that routine vaccinations may have non-specific effects on child mortality; measles vaccine (MV) is associated with lower mortality and diphtheria-tetanus-pertussis (DTP) with relatively higher mortality. We used data from Navrongo, Ghana, to examine the impact of vaccinations on child mortality., Methods: Vaccination status was assessed at the initiation of a trial of vitamin A supplementation and after 12 and 24 months of follow-up. Within the placebo group, we compared the mortality over the first 4 months and the full 2 years of follow-up for different vaccination status groups with different likelihoods of additional vaccinations during follow-up. The frequency of additional vaccinations was assessed among children whose vaccination card was seen at 12 and 24 months of follow-up., Results: Among children with a vaccination card, more than 75% received missing DTP or MV during the first 12 months of follow-up, whereas only 25% received these vaccines among children with no vaccination card at enrollment. Children without a card at enrollment had a significant threefold higher mortality over the 2-year follow-up period than those fully vaccinated. The small group of children with DTP3-4 but no MV at enrollment had lower mortality than children without a card and had the same mortality as fully vaccinated children. In contrast, children with 1-2 DTP doses but no MV had a higher mortality during the first 4 months than children without a card [MRR = 1.65 (0.95, 2.87)]; compared with the fully vaccinated children, they had significantly higher mortality after 4 months [MRR = 2.38 (1.07, 5.30)] and after 2 years [MRR = 2.41 (1.41, 4.15)]. Children with 0-2 DTP doses at enrollment had higher mortality after 4 months (MRR = 1.67 (0.82, 3.43) and after 2 years [MRR = 1.85 (1.16, 2.95)] than children who had all three doses of DTP at enrollment., Conclusions: As hypothesised, DTP vaccination was associated with higher child mortality than measles vaccination. To optimise vaccination policies, routine vaccinations need to be evaluated in randomised trials measuring the impact on survival., (© 2012 Blackwell Publishing Ltd.)

Objectives: To compare (i) side effects associated with the simultaneous adminstration of praziquantel, albendazole and ivermectin with side affects associated with albendazole and ivermectin only and (ii) coverage by volunteers distributing three or two drugs., Methods: Two-arm comparative study in northern Ghana integrated praziquantel distribution into an existing lymphatic filariasis and onchocerciasis control programme using Community Directed Distributors. The control arm continued to distribute only ivermectin and albendazole. Dosages of ivermectin and praziquantel were based on height. Treatment was directly observed, and all two/three drugs were co-administered. Adverse effects were recorded based on passive surveillance. Parasitological, anthropometric and haematological data were collected at baseline., Results: Prevalence of Schistosoma haematobium infection among 1001 (boys: 47.9% girls: 52.1%) school-age children (6-15 years) [intervention: 30.0% (CI: 23.1-34.2); control: 23.0% (CI: 18.9-27.0)], mean haemoglobin, weight and age were similar among the intervention and control groups. While 1676 (99.1%) compounds in the control area were visited and 15,020 (96.58%) people were treated, only 1375 (88.5%) compounds in the intervention area were visited and 8454 (80.97%) people treated (P < 0.001). The numbers of adverse effects were similar (intervention: 50/6896; control: 130/15,020). The most reported adverse effects was headache (intervention: 14/50; control: 13/130), followed by body weakness, which was reported more from the intervention group (intervention: 13/50, 95% CI: 14.6-40.3; control: 6/130, 95% CI: 1.7-9.8]. Sixty-six per cent (6896/10,441) of the eligible population received praziquantel., Conclusions: Reported adverse events were mild and managed at the subdistrict level with no cases of hospitalization; intensive health education will, however, be required to improve coverage., (© 2011 Blackwell Publishing Ltd.)

Objective: To determine the impact of deploying nurses and volunteers to village locations on demographic and health outcomes., Method: We implemented an experimental design that emphasizes the value of aligning community health services with traditional social institutions that organize village life. Data for this analysis come from the Navrongo demographic surveillance system, a longitudinal database that tracks fertility, mortality, and migration events over time. The experiment uses conventional demographic methods for estimating mortality rates from longitudinal demographic surveillance registers., Results: Posting nurses to community locations reduced childhood mortality rates by over half in 3 years and accelerated attainment of the childhood-survival millennium development goal (MDG) in the study areas relative to trends observed in comparison areas., Conclusion: Results from the Navrongo experiment demonstrate that community health and family planning programmes can have an impact on childhood mortality. Posting nurses to communities can dramatically accelerate the pace of progress in achieving the childhood-survival MDGs. Community-volunteer approaches, however, have no additional impact, a finding that challenges the child survival value of international investment in volunteer-based health programmes. The total cost of the intensive arm of the project is less than $10 per capita per year. Navrongo research thus demonstrates affordable means of attaining the child survival MDG agenda with existing technologies.

Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.

Molecular genotyping of baseline and post-treatment recurrent Plasmodium falciparum is recommended to distinguish recrudescent from new infections. However, genotyping performance and adjustment of treatment outcomes have not been evaluated in large field trials. Parasitological outcomes were assessed in nine double-blinded trials of uncomplicated P. falciparum malaria in African children treated with artesunate/placebo plus standard monotherapies. Day 28 failure rates were adjusted by stepwise genotyping the P. falciparum glutamate rich protein (glurp), merozoite surface protein 1 (msp1) and 2 (msp2). We calculated overall and laboratory genotyping performance and compared unadjusted (crude) and PCR-adjusted outcomes. 3455 (93.6%) of 3691 enrolled patients were evaluable by Day 28. 767 (22%) had post-Day 14 recurrent parasitemias of which 686 could be genotyped: 246 were recrudescences, 286 new infections and 154 unresolved. The overall and laboratory genotyping performance were 69 (12-100)% and 78 (50-100)%, respectively. The mean Day 28 crude parasitological failure rate was 44 (range 3-87)%. PCR-adjusted rates were 36 (range 2-86)% if unresolved infections were counted as failures or 33 (range 2-86)% if excluded from analysis. The overall difference between crude Day 28 and Day 14 failure rates was 22% (95% CI 20.3, 24.6) but decreased to 14% (95% CI 12.1, 16.3) if unresolved infections are counted as failures, or to 11% (95% CI 9.8, 16.3) if unresolved infections are excluded from the analysis. Genotyping refined treatment outcomes but diligence is needed in sample collection and analysis to improve its performance. Our findings support the WHO recommendation of PCR genotyping in malaria clinical trials and suggest that stepwise genotyping of only two loci (msp2 and msp1 or glurp) can reliably discriminate recrudescences from new infections.

Objectives: To describe the trend and causes of neonatal deaths in a rural district in northern Ghana., Methods: Descriptive analysis of data collected from the Navrongo Demographic Surveillance System and verbal autopsies conducted on all neonatal deaths from 1995-2002., Results: Of 1118 recorded neonatal deaths 1068 (95.5%) could be analysed. Only 13.2% of deaths occurred at the health facility; 62.7% occurred in the early neonatal period, with prematurity (38%) and birth injuries (19%) as leading causes. Infectious causes (66%) were the major contributors to late neonatal deaths. Infanticide accounted for 4.9% of all neonatal deaths. The cause-specific mortality rate for neonatal tetanus remained under 2.5% throughout the 8-year period. Overall, the neonatal mortality rate declined at an average of 2.5 per 1000 live births per year: Down by nearly 50% from 40.9 (95%C.I. 34.1-46.8) in 1995 to 20.5 (95%C.I.17.3-22.7) in 2002., Conclusion: The various health interventions undertaken in this district have had the collateral effect of causing decline in neonatal mortality. Neonatal mortality could be further reduced by preventing and treating neonatal infections, having skilled attendance at delivery and the elimination of infanticide. Data from demographic surveillance sites may be useful in monitoring trends in child mortality.

A cohort of 197 adults in Kassena-Nankana District (northern Ghana) was radically cured of malaria parasites to study subsequent incidence of malaria infection. During the following 20 weeks of the malaria transmission season, 49% experienced clinical attacks associated with Plasmodium falciparum parasitaemia. In a group of 202 adults identically followed-up 1 year later without being treated, only 38% experienced such episodes (log-rank test for equality of survivor functions, P=0.035). Clinical attacks in radically cured individuals presented with lower parasite densities but more symptoms. Randomized studies are needed to test the hypothesis that radical cure of P. falciparum enhances the risk and severity of subsequent clinical malaria attacks.

A community-based randomized, controlled trial of permethrin impregnated bednets was carried out in a rural area of northern Ghana, between July 1993 and June 1995, to assess the impact on the mortality of young children in an area of intense transmission of malaria and no tradition of bednet use. The district around Navrongo was divided into 96 geographical areas and in 48 randomly selected areas households were provided with permethrin impregnated bednets which were re-impregnated every 6 months. A longitudinal demographic surveillance system was used to record births, deaths and migrations, to evaluate compliance and to measure child mortality. The use of permethrin impregnated bednets was associated with 17% reduction in all-cause mortality in children aged 6 months to 4 years (RR = 0.83; 95% CI 0.69-1.00; P = 0.05). The reduction in mortality was confined to children aged 2 years of younger, and was greater in July-December, during the wet season and immediately after (RR = 0.79; 95% CI 0.63-1.00), a period when malaria mortality is likely to be increased, than in the dry season (RR = 0.92, 95% CI 0.73-1.14). The ready acceptance of bednets, the high level of compliance in their use and the subsequent impact on all-cause mortality in this study has important implications for programmes to control malaria in sub-Saharan Africa.