Norbert Georg Schwarz

Placental Malaria Increases Malaria Risk in the First 30 Months of Life

BACKGROUND Plasmodium falciparum infection during pregnancy is associated with stillbirth, fetal growth restriction, and low birth weight. An additional consequence may be increased risk of malaria in early life, although the epidemiological evidence of this consequence is limited. METHODS A cohort of 527 children were observed actively every month for 30 months after delivery. Offspring of mothers with microscopically detectable placental P. falciparum infection at the time of delivery were defined as exposed. The outcome measure was malaria (parasitemia and fever). Analyses were performed using Cox proportional hazard models and were stratified by gravidity. RESULTS Overall, offspring of mothers with placental P. falciparum infection had a significantly higher risk of clinical malaria during the first 30 months of life (adjusted hazard ratio, 2.1; 95% confidence interval [CI], 1.2-3.7). The adjusted hazard ratio for offspring of multigravidae was 2.6 (95% CI, 1.3-5.3), and that for primigravidae was 1.5 (95% CI, 0.6-3.8). The offspring of placenta-infected primigravidae had no episodes of malaria during the first year of life. CONCLUSIONS Our findings show that active placental P. falciparum infection detected at delivery is associated with an approximately 2-fold greater risk of malaria during early life, compared with noninfection. The fact that persons born to infected multigravidae rather than primigravidae appear to be at greater risk emphasizes the importance of preventing malaria in mothers of all gravidities.

National health insurance coverage and socio‐economic status in a rural district of Ghana

Objective  To explore the association between socio‐economic status (SES) and health insurance subscription to the Ghanaian National Health Insurance Scheme (NHIS) of residents of the Asante Akim North district of the Ashanti Region, Ghana.

Intermittent Preventive Treatment against Malaria in Infants in Gabon-A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND Intermittent preventive treatment aims to maximize the protective effects of malaria chemoprophylaxis while minimizing the deleterious effects. METHODS In Gabon, 1189 infants received either sulfadoxine-pyrimethamine (SP; 250 and 12.5 mg, respectively) or placebo at 3, 9, and 15 months of age. Children were actively followed-up until 18 months of age. RESULTS In the intention-to-treat population at 18 months of follow-up, 84 children (17%) in the SP group had > or =1 episode of anemia, versus 108 (21%) in the placebo group (protective efficacy, 22% [95% confidence interval {CI}, -1% to 40%]; P=.06). In the intervention group, there were 66 episodes during 485 person-years at risk, compared with 79 episodes during 497 years in the placebo group (protective efficacy, 17% [95% CI, -24% to 45%; P=.36). The effects were similar at 12 months of follow-up. The study drug was safe and well tolerated. CONCLUSIONS The intervention was efficacious, producing a reduction in risk for anemia but a smaller effect against malaria. It is a valuable additional tool to control malaria in a highly vulnerable age group. Remaining important questions are currently being addressed in further studies. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00167843.

Incidence and Characteristics of Bacteremia among Children in Rural Ghana

The objective of the study was to describe systemic bacterial infections occurring in acutely ill and hospitalized children in a rural region in Ghana, regarding frequency, incidence, antimicrobial susceptibility patterns and associations with anthropometrical data. Blood cultures were performed in all children below the age of five years, who were admitted to Agogo Presbyterian Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009. Medical history and anthropometrical data were assessed using a standardized questionnaire at admission. Incidences were calculated after considering the coverage population adjusted for village-dependent health-seeking behavior. Among 1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%; n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%; n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of bacteremia was 46.6 cases/1,000 (CI 40.9–52.2). Yearly cumulative incidences per 1,000 of the four most frequent isolates were 25.2 (CI 21.1–29.4) for NTS, 6.3 (CI 4.1–8.4) for S. aureus, 4.3 (CI 2.5–6.1) for S. pneumoniae and 3.3 (CI 1.8–4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia and systemic NTS bloodstream infection. Children older than three months had more often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100% of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic bacterial infections in nearly 20% of hospitalized children underline the need for microbiological diagnostics, to guide targeted antimicrobial treatment and prevention of bacteremia. If microbiological diagnostics are lacking, calculated antimicrobial treatment of severely ill children in malaria-endemic areas should be considered.

Principal component analysis of socioeconomic factors and their association with malaria in children from the Ashanti Region, Ghana.

BackgroundThe socioeconomic and sociodemographic situation are important components for the design and assessment of malaria control measures. In malaria endemic areas, however, valid classification of socioeconomic factors is difficult due to the lack of standardized tax and income data. The objective of this study was to quantify household socioeconomic levels using principal component analyses (PCA) to a set of indicator variables and to use a classification scheme for the multivariate analysis of children < 15 years of age presented with and without malaria to an outpatient department of a rural hospital.MethodsIn total, 1,496 children presenting to the hospital were examined for malaria parasites and interviewed with a standardized questionnaire. The information of eleven indicators of the familys housing situation was reduced by PCA to a socioeconomic score, which was then classified into three socioeconomic status (poor, average and rich). Their influence on the malaria occurrence was analysed together with malaria risk co-factors, such as sex, parents educational and ethnic background, number of children living in a household, applied malaria protection measures, place of residence and age of the child and the mother.ResultsThe multivariate regression analysis demonstrated that the proportion of children with malaria decreased with increasing socioeconomic status as classified by PCA (p < 0.05). Other independent factors for malaria risk were the use of malaria protection measures (p < 0.05), the place of residence (p < 0.05), and the age of the child (p < 0.05).ConclusionsThe socioeconomic situation is significantly associated with malaria even in holoendemic rural areas where economic differences are not much pronounced. Valid classification of the socioeconomic level is crucial to be considered as confounder in intervention trials and in the planning of malaria control measures.

Typhoid Fever among Children, Ghana

To the Editor: Typhoid fever (TF) remains a problem of concern in many low-income countries. Salmonella enterica serovar Typhi causes ≈22,000,000 symptomatic infections and 220,000 fatalities worldwide annually (1). However, the effect and incidence of TF in many parts of sub-Saharan Africa are largely unknown because diagnostic laboratories are lacking and fatal TF is frequently attributed to malaria (2,3). In Ghana, TF ranks among the leading 20 causes of outpatient illness, accounting for 0.92% of hospital admissions (4). We conducted our study at the rural Agogo Presbyterian Hospital in the Ashanti Region of Ghana. The percentage of residents of 99 villages and household clusters of buildings (population size 18–13,559 persons, median 277 persons) with access to the study hospital was assessed in a healthcare utilization survey. A proportional-to-size number of children were randomly selected in each village, and a standardized interview was conducted. TF incidences were calculated for September 2007–November 2008 (Table). A bacteriology laboratory with BACTEC 9050 automated blood culture system (Becton Dickinson, Sparks, MD, USA) was established in the study hospital and run to assess the number of admissions with TF, the incidence of TF in the adjoining community and S. enterica ser. Typhi resistance to a panel of antimicrobial drugs. Table Estimates of Salmonella enterica serovar Typhi incidence in children, Ghana, September 2007–November 2008 The study included 1,456 children <15 years of age who were admitted to the pediatric ward of Agogo Presbyterian Hospital over the 23-month study period. Overall, 52.1% were male; mean age of children was 32.2 months (SD ± 36.0 months; median 19 months, range 0–174 months). Blood was cultured by using a BACTEC 9050 blood culture system (Becton Dickinson), and positive samples were examined by standard methods. Antimicrobial drug susceptibility testing was performed on all serovar Typhi isolates by using the Kirby-Bauer disk-diffusion method for ampicillin, chloramphenicol, tetracycline, trimethoprim/sulfamethoxazole, amoxicillin/clavulanic acid, gentamicin, ciprofloxacin, and ceftriaxone. Children <2 years of age had the highest proportion of positive blood cultures (164/1,456, 21.3%; Figure A1). Of 298 blood cultures yielding positive growth for bacterial pathogens or for Candida spp., 37 (12.4%) isolates (2.5% of the 1,456 hospitalized children) were positive for S. enterica ser. Typhi. The frequency of TF was low among children <2 years of age (7/1,018, 0.7%), increased among those 2 to <11 years of age (29/417, 7.0%), and decreased among children ≥11 years of age (1/22, 4.6%) (Figure A1). One (2.7%) child with TF died. Malaria parasites were detected in 2 children with S. enterica ser. Typhi. Pathogens other than S. enterica ser. Typhi were identified among 21.3% and 11.8% of children 0 to <2 years and 5 to <8 years of age, respectively. These pathogens included nontyphoidal salmonellae, Staphylococcus aureus, and Streptococcus pneumoniae. S. enterica ser. Typhi isolates were resistant to chloramphenicol (73%), trimethoprim/sulfamethoxazole (71%), ampicillin/amoxicillin (70%), tetracycline (64%), gentamicin (46%), and amoxicillin/clavulanic acid (24%) but susceptible to ciprofloxacin and ceftriaxone. TF incidence in children <5 years of age was ≈190 cases/100,000 population and highest in children 2–5 years of age (290/100,000 per year) and 5–8 years of age (200/100,000 per year) (Table). In children older than 8, incidence decreased continuously, and the number of cases was too low to enable precise age-stratified incidence calculations. The incidences in the study area point to a higher impact of TF than expected (4) and may reflect an underestimation of TF in other West African regions as well. Our high incidence figure may still underestimate the incidence because of a low sensitivity of standard microbiologic methods (up to 50%), which are prone to underdiagnose moderate bacteremia in Salmonella infections (5,6). Compared with Asia, only limited data are available from Africa on S. enterica ser. Typhi drug resistance. A study from Nigeria showed that, among serovar Typhi strains isolated from hospitalized patients in Lagos during 1997–2004, resistance rates reached 87% for ampicillin and were 0.7% for ciprofloxacin, compared with 70% and 0%, respectively, in the present study. Resistance to trimethoprim/sulfamethoxazole was 59% in Nigeria, compared with 71% in Ghana. In Togo, proportions of serovar Typhi strains resistant to chloramphenicol and trimethoprim/sulfamethoxazole were 33% and 46%, respectively, before 2002 and 73% and 79% in 2003–2004 (7) and thus similar to those in our study. In addition, resistances to ciprofloxacin and ceftriaxone were <10%. Multidrug resistance (resistance to ampicillin, trimethoprim/sulfamethoxazole, and chloramphenicol) was observed in 63% of children in our study, compared with 7% in India, 22% in Vietnam, and 65% in Pakistan (8–10). More effort is needed in Africa to enable reliable and standardized laboratory diagnoses of Salmonella infections and to sustain TF surveillance and drug sensitivity surveys. Moreover, introduction of a vaccination program should be discussed after more data are obtained from other areas in Ghana and West Africa. Such data currently are collected in an extensive standardized surveillance program across the continent performed by our group and others. In parallel, trials should be conducted to assess the effectiveness and cost-effectiveness of currently available and newly developed TF vaccines.

Clinical and Parasitological Characteristics of Puerperal Malaria

BACKGROUND Women with semi-immunity to malaria who live in regions where the disease is endemic are at increased risk for more frequent and severe episodes of malaria during pregnancy. Recent findings indicate that this increased risk might persist beyond delivery, but the underlying mechanisms for this change in risk are poorly understood. METHODS One hundred fifty women were included in a cohort study in Lambaréné, Gabon, and were actively followed up weekly for 10 weeks after delivery, as were nonpregnant control women who had been matched to them by location and age. Parasites in samples of placenta and blood were genotyped by use of polymerase chain reaction amplification of the merozoite surface antigen 2 gene and the subtelomeric variable open reading frame gene of Plasmodium falciparum. RESULTS Eleven puerperal women had cases of clinical malaria, compared with 1 control woman (rate ratio, 9.8; P=.006). Eighteen puerperal women had P. falciparum parasitemia, compared with 6 control women (rate ratio, 2.7; P=.03). Five of 16 puerperal women (31%) with parasitemia on follow-up had identical parasites in their placentas and blood, and 11 of these cases (69%) were the result of reinfection. Puerperal women remained at equal risk for the development of parasitemia throughout the first 10 weeks after delivery. Use of bed nets, use of chloroquine prophylaxis during pregnancy, presence of malaria episodes during pregnancy, gravidity, and age were not associated with the acquisition of parasitemia during follow-up. CONCLUSIONS Compared with nonpregnant women, puerperal women have a considerably increased risk for the development of malaria and/or parasitemia. This increased risk is caused both by the recurrence of P. falciparum parasitemia and by the increased susceptibility to new infections, although the latter plays a more significant role.

Socio-economic status is inversely related to bed net use in Gabon

BackgroundInsecticide-treated bed nets (ITNs) range among the most effective measures of malaria prophylaxis, yet their implementation level in sub-Saharan Africa is still low. The goal of this study was to investigate the influence of socio-economic factors on the use of bed nets by mothers in Gabon.MethodsA cross-sectional study was conducted completing pre-tested, interviewer-administered questionnaires exploring socioeconomic proxy measures with 397 mothers or guardians of young children. Respondents were grouped according to their socio-economic situation, using scores. The condition of the bed nets was evaluated during a home visit.ResultsSocio-economic factors of wellbeing were negatively associated with bed net use, such as living in a stone house (OR 0.26, 95% CI 0.14–0.48), running water in the house (OR 0.44, 95% CI 0.21–0.92), shower/flush toilet in the house (OR 0.39/0.34, 95% CI 0.21–0.75/0.16–0.73), ownership of a freezer (OR 0.50, 95% CI 0.26–0.96) and belonging to the highest group in the economic score (OR 0.32, 95% CI 0.15–0.67). In contrast, similar factors were positively associated with a good maintenance condition of the bed nets: higher monthly income (OR 5.64, 95% CI 2.41–13.19) and belonging to the highest group in the economic score (OR 2.55, 95% CI 1.19 – 5.45).ConclusionAmong the poorest families in Lambaréné the coverage with untreated nets (UTNs) is the highest, but the condition of these UTNs is the worst. To achieve a broad implementation of ITNs in Lambaréné, there is an urgent need for educational programmes as well as need-tailored marketing strategies for ITNs.

Artesunate – amodiaquine combination therapy for falciparum malaria in young Gabonese children

BackgroundArtesunate-amodiaquine combination for the treatment of childhood malaria is one of the artemisinin combination therapies (ACTs) recommended by National authorities in many African countries today. Effectiveness data on this combination in young children is scarce.MethodsThe effectiveness of three daily doses of artesunate plus amodiaquine combination given unsupervised (n = 32), compared with the efficacy when given under full supervision (n = 29) to children with falciparum malaria were assessed in an unrandomized study.Results61 patients analysed revealed a PCR-corrected day-28 cure rate of 86 % (25 of 29 patients; CI 69 – 95 %) in the supervised group and 63 % (20 of 32 patients; CI 45 – 77 %) in the unsupervised group. The difference in outcome between both groups was statistically significant (p = 0.04). No severe adverse events were reported.ConclusionThe effectiveness of this short course regimen in young children with falciparum malaria could be augmented by increased adherence and improved formulation.

Modeling the Relationship between Precipitation and Malaria Incidence in Children from a Holoendemic Area in Ghana

Climatic factors influence the incidence of vector-borne diseases such as malaria. They modify the abundance of mosquito populations, the length of the extrinsic parasite cycle in the mosquito, the malarial dynamics, and the emergence of epidemics in areas of low endemicity. The objective of this study was to investigate temporal associations between weekly malaria incidence in 1,993 children < 15 years of age and weekly rainfall. A time series analysis was conducted by using cross-correlation function and autoregressive modeling. The regression model showed that the level of rainfall predicted the malaria incidence after a time lag of 9 weeks (mean = 60 days) and after a time lag between one and two weeks. The analyses provide evidence that high-resolution precipitation data can directly predict malaria incidence in a highly endemic area. Such models might enable the development of early warning systems and support intervention measures.