Non-falciparum malaria infections in pregnant women in West Africa.

BACKGROUND: Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. METHODS: Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a non-falciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. RESULTS: P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. CONCLUSIONS: Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites.

A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy.

BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach. METHODS AND FINDINGS: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. CONCLUSIONS: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122.

Olfactory hallucination in childhood primary headaches: case series.

BACKGROUND: Although olfactory hallucination (OH) has been reported in patients with primary headaches, olfactory aura has not been recognised by the International Classification of Headache Disorders (ICHD-2). In this study, we examined the frequency and characteristics of OH among children and adolescents with primary headaches. METHODS: 839 neurologically normal patients with primary headaches (537 migraine) were eligible for the assessment of olfactory hallucination. Headache diagnosis was based on the ICHD. Data were prospectively collected during clinic sessions and using headache diaries. RESULTS: Olfactory hallucination was reported exclusively during headache attacks by 21/839 (2.5%) patients, all of whom had migraine. The prevalence of olfactory hallucination was 3.9% among migraineurs (6.5% among those with migraine aura). Olfactory hallucination shortly followed the onset of headaches and lasted from 15 to 50 minutes. Of those with MA, 10 patients had visual aura; two had somatosensory aura; one had motor aura; and two had a combination of visual and somatosensory aura. Using the ICHD-2, both OH and migraine aura occurred in the same headache attacks. In 12/15 patients, OH occurred simultaneously with migraine aura, whereas in 3/12 patients, it preceded aura. CONCLUSION: Our findings show that olfactory hallucination occurs in migraine and it has similarities to migraine aura.

Two strategies for the delivery of IPTc in an area of seasonal malaria transmission in the Gambia: a randomised controlled trial.

BACKGROUND: The Expanded Programme on Immunisation (EPI) provides an effective way of delivering intermittent preventive treatment for malaria (IPT) to infants. However, it is uncertain how IPT can be delivered most effectively to older children. Therefore, we have compared two approaches to the delivery of IPT to Gambian children: distribution by village health workers (VHWs) or through reproductive and child health (RCH) trekking teams. In rural areas, RCH trekking teams provide most of the health care to children under the age of 5 years in the Infant Welfare Clinic, and provide antenatal care for pregnant women. METHODS AND FINDINGS: During the 2006 malaria transmission season, the catchment populations of 26 RCH trekking clinics in The Gambia, each with 400-500 children 6 years of age and under, were randomly allocated to receive IPT from an RCH trekking team or from a VHW. Treatment with a single dose of sulfadoxine pyrimethamine (SP) plus three doses of amodiaquine (AQ) were given at monthly intervals during the malaria transmission season. Morbidity from malaria was monitored passively throughout the malaria transmission season in all children, and a random sample of study children from each cluster was examined at the end of the malaria transmission season. The primary study endpoint was the incidence of malaria. Secondary endpoints included coverage of IPTc, mean haemoglobin (Hb) concentration, and the prevalence of asexual malaria parasitaemia at the end of malaria transmission period. Financial and economic costs associated with the two delivery strategies were collected and incremental cost and effects were compared. A nested case-control study was used to estimate efficacy of IPT treatment courses. Treatment with SP plus AQ was safe and well tolerated. There were 49 cases of malaria with parasitaemia above 5,000/µl in the areas where IPT was delivered through RCH clinics and 21 cases in the areas where IPT was delivered by VHWs, (incidence rates 2.8 and 1.2 per 1,000 child months, respectively, rate difference 1.6 [95% confidence interval (CI) -0.24 to 3.5]). Delivery through VHWs achieved a substantially higher coverage level of three courses of IPT than delivery by RCH trekking teams (74% versus 48%, a difference of 27% [95% CI 16%-38%]). For both methods of delivery, coverage was unrelated to indices of wealth, with similar coverage being achieved in the poorest and wealthiest groups. The prevalence of anaemia was low in both arms of the trial at the end of the transmission season. Efficacy of IPTc against malaria during the month after each treatment course was 87% (95% CI 54%-96%). Delivery of IPTc by VHWs was less costly in both economic and financial terms than delivery through RCH trekking teams, resulting in incremental savings of US$872 and US$1,244 respectively. The annual economic cost of delivering at least the first dose of each course of IPTc was US$3.47 and US$1.63 per child using trekking team and VHWs respectively. CONCLUSIONS: In this setting in The Gambia, delivery of IPTc to children 6 years of age and under by VHWs is more effective and less costly than delivery through RCH trekking clinics. TRIAL REGISTRATION: ClinicalTrials.gov NCT00376155. Please see later in the article for the Editors' Summary.

A randomised trial to compare the safety, tolerability and efficacy of three drug combinations for intermittent preventive treatment in children.

BACKGROUND: Results from trials of intermittent preventive treatment (IPT) in infants and children have shown that IPT provides significant protection against clinical malaria. Sulfadoxine-pyrimethamine (SP) given alone or in combination with other drugs has been used for most IPT programmes. However, SP resistance is increasing in many parts of Africa. Thus, we have investigated whether SP plus AQ, SP plus piperaquine (PQ) and dihydroartemisinin (DHA) plus PQ might be equally safe and effective when used for IPT in children in an area of seasonal transmission. METHODS: During the 2007 malaria transmission season, 1008 Gambian children were individually randomized to receive SP plus amodiaquine (AQ), SP plus piperaquine (PQ) or dihydroartemisinin (DHA) plus PQ at monthly intervals on three occasions during the peak malaria transmission season. To determine the risk of side effects following drug administration, participants in each treatment group were visited at home three days after the start of each round of drug administration and a side effects questionnaire completed. To help establish whether adverse events were drug related, the same questionnaire was administered to 286 age matched control children recruited from adjacent villages. Morbidity was monitored throughout the malaria transmission season and study children were seen at the end of the malaria transmission season. RESULTS: All three treatment regimens showed good safety profiles. No severe adverse event related to IPT was reported. The most frequent adverse events reported were coughing, diarrhoea, vomiting, abdominal pain and loss of appetite. Cough was present in 15.2%, 15.4% and 18.7% of study subjects who received SP plus AQ, DHA plus PQ or SP plus PQ respectively, compared to 19.2% in a control group. The incidence of malaria in the DHA plus PQ, SP plus AQ and SP plus PQ groups were 0.10 cases per child year (95% CI: 0.05, 0.22), 0.06 (95% CI: 0.022, 0.16) and 0.06 (95% CI: 0.02, 0.15) respectively. The incidence of malaria in the control group was 0.79 cases per child year (0.58, 1.08). CONCLUSION: All the three regimens of IPT in children were safe and highly efficacious TRIAL REGISTRATION: ClinicalTrials.gov NCT00561899.

Transcutaneous bilirubin measurements and serum total bilirubin levels in indigenous African infants.

OBJECTIVE: The objective of this study was to determine whether transcutaneous bilirubin (TcB) measurements correlate with serum total bilirubin (STB) levels in indigenous, darkly pigmented African newborns with varying degrees of skin pigmentation, some of which had developed kernicterus. METHODS: Jaundiced infants who were < or =2 weeks of age and admitted to Baptist Medical Center-Eku (Eku; n = 29) and Jos University Teaching Hospital (Jos; n = 98) in Nigeria were studied. TcB measurements using the BiliChek were made simultaneously with blood sampling for STB measurements by spectrophotometry before phototherapy. RESULTS: Using linear regression analysis, we found that measurements of TcB correlated well with those of STB with r values of.90 and.88 for Eku and Jos, respectively. Mean bias and imprecision of TcB measurements as compared with STB measurements for the total population was 0.5 +/- 7.6 mg/dL using the method of Bland and Altman. At STB > or 12 mg/dL, correlation (r =.84) and bias and imprecision (-1.2 +/- 8.6 mg/dL) of measurements were only slightly poorer. Furthermore, when infants were grouped by degree of skin pigmentation, correlations of TcB and STB measurements remained strong. CONCLUSIONS: From these results, we can conclude that TcB measurements are a useful and reliable index for estimating STB levels in pigmented neonates, including those with hyperbilirubinemia and kernicterus. In the absence of reliable STB measurements, the relatively simple and noninvasive TcB measurements can be an important adjunct in directing phototherapy and exchange transfusions, thereby preventing bilirubin-induced morbidity and mortality in low-technology clinical environments.

Promoting the exclusive feeding of own mother's milk through the use of hindmilk and increased maternal milk volume for hospitalized, low birth weight infants (< 1800 grams) in Nigeria: a feasibility study.

A feasibility study was used to determine (1) if hindmilk feedings of own mother's milk, as reported in the United States, could be instituted in a Nigerian neonatal intensive care unit and result in adequate infant weight gain without exogenous additives; and (2) if the use of a hospital-grade electric breast pump to separate foremilk from hindmilk was feasible in this setting. Mean weight gain for 16 preterm infants during the hindmilk intervention (18.8 g/d) exceeded intrauterine standards without the use of exogenous substances. At the time of hospital discharge, mean maternal daily milk volume was 342 mL/kg/d, indicating that the infants, on average, had 90% more milk available to them than they required. Mean infant weight gains were 14.2 and 16.6 g/d from 1 to 7 and 8 to 23 (x = 14.8) days postdischarge, respectively. Therefore, hindmilk feedings are effective and feasible for hospitalized, low birth weight infants in developing countries, and lactation specialists may use our protocol for further research.