Dosage for malaria treatment

In 1998, the Kenyan Ministry of Health introduced intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), one treatment dose in the second trimester (16-27 weeks) and one treatment dose between 28 and 34 weeks of gestational age, for the control of malaria in pregnancy. We evaluated the coverage and determinants of receipt of IPT after its introduction in the Provincial Hospital in Kisumu, western Kenya. Information on the use of IPT in pregnancy was collected from women who attended the antenatal clinic (ANC) and delivered in the same hospital. In exit interviews, we assessed patterns of IPT use in the ANC. Of 1498 women who delivered between June 1999 and June 2000, 23.7%, 43.4% and 32.9% received > or =2, 1 or no dose of SP, respectively. Late first ANC attendance was the most important factor contributing to incomplete IPT; 45% of the women started attending ANC in the third trimester. More women received at least one tetanus toxoid immunization than at least one dose of IPT (94%vs. 67%, P < 0.05). In exit interviews, 74% correctly associated IPT with treatment of malaria; however, knowledge on the need for the second dose was poor. Three per cent of the administrations were given despite contraindications. The agreement between gestational age by date of last menstrual period and by palpation was low (kappa = 0.1). Education of pregnant women and ANC staff to increase earlier attendance for ANC has the potential to substantially increase the proportion of women receiving two doses of IPT with SP.

BackgroundIn respect of the WHO’s commendation to incorporate traditional medicine (TM) in health care, the Cameroon government wants to promote the use of the traditional medicine and is resolute on encouraging the treatment of patients with alternative medicine from traditional sources. This study explores the use of herbal tea by Cameroonian adults to prevent or treat diseases and the socio-demographic determinants of tea use among participants.MethodsA cross-sectional survey was conducted among 307 Cameroonian adults (18–65 years) randomly selected within 4 hospitals and 4 communities in the Centre and Southwest regions of Cameroon between 04/01–20/04/2022, using interviewer administered semi-structured questionnaires. Binary logistic regression analysis was conducted to determine the association between variables.ResultsOver four-fifth (89.3%) of participants had taken herbal teas at least once within the last 2 years prior to the survey, and most participants used the teas for the prevention and treatment of Covid-19 (67.9%), malaria (59.7%) and typhoid fever (35%). Most respondents took the teas warm (75%), and the treatment dosage used by most respondents (51%) was “one glass in the morning and evening for one to two weeks”. The teas taken by 70% of users had bad or bitter taste and 52.2% of them were uncomfortable with the bad taste. However, the majority of users completed their treatment dosage (72%), 90.5% of them were willing to use teas for treatment if prescribed in health facilities in future, and 90.1% were in support that herbal teas should be prescribed in hospitals. There was no significant association (p ≥ 0.05) between sociodemographic characteristics of participants and herbal tea use. However, the major motivating factor for acceptability of herbal tea use was treatment effectiveness (52.7%).ConclusionThere is high prevalence of herbal tea use among adults Cameroonians in the studied settings in the Centre and Southwest regions of Cameroon, with a positive opinion and willingness to use teas if prescribed in health facilities. Authorities must ensure the effectiveness and safety of traditional medicine served in health facilities, to enhance compliance and adequate use.

Integrated approach to child health in developing countries

Antenatal interventions to reduce risk of low birth weight related to maternal infections during pregnancy

SummaryHydroxychloroquine was given orally to 50 patients with P. vivax infections, either in a single dose or in a one-day treatment of several doses. Both parasitemia and temperature were controlled on the average in less than 2 days, with no unfavorable effects noted. This study in Venezuela confirms observations by others that hydroxychloroquine exhibits antimalarial activity against P. vivax comparable to that of other 4-aminoquinolines but appears to be better tolerated.

Malaria intermittent preventive treatment in infants, chemoprophylaxis, and childhood vaccinations

Mefloquine is one of the drugs approved by the FDA for malaria chemoprophylaxis. Mefloquine is also approved for the treatment of malaria and is widely used for this purpose in combination with artesunate. However, the clinical utility of the compound has been compromised by reports of adverse neurological effects in some patients. In the present study, the potential neurological effects of mefloquine were investigated with six 7-week-old female rats given a single oral dose of the compound. Potential mefloquine-induced neurological effects were monitored using a standard functional observational battery, automated open field tests, automated spontaneous activity monitoring, a beam traverse task, and histopathology. Plasma mefloquine concentrations were determined 72 h after dosing by using liquid chromatography-mass spectrometry. Mefloquine induced dose-related changes in endpoints associated with spontaneous activity and impairment of motor function and caused degeneration of specific brain stem nuclei (nucleus gracilis). Increased spontaneous motor activity was observed only during the rats' normal sleeping phase, suggesting a correlate to mefloquine-induced sleep disorders. The threshold dose for many of these effects was 187 mg/kg of body weight. This dose yielded plasma mefloquine concentrations after 72 h that are similar to those observed in humans after the treatment dose. Collectively, these data suggest that there may be a biological basis for some of the clinical neurological effects associated with mefloquine.

Malaria is one of the major infectious diseases that remains a constant challenge to human being mainly due to the emergence of drug-resistant strains of parasite and also the availability of drugs, which are non-specific for their pharmacodynamic activity and known to be associated with multiple side effects. The disease has acquired endemic proportions in tropical countries where the hygienic conditions are not satisfactory while the environmental conditions favor the proliferation of parasite and its transmission, particularly through the female anopheles. It is obvious that to square up the problems, there is a need for designing and development of more effective drugs, which can combat the drug-resistant strains of the parasite. Molecular biology of the parasite and its homing into host cellular tropics provide multiple drug targets that could judiciously be considered for engineering and designing of new generation antimalarial drugs and also drug delivery systems. Though the recent reports document that against malaria parasite the vaccine could be developed, nevertheless, due to smart mutational change overs by the parasite, it is able to bypass the immune surveillance. The developed vaccine therefore failed to assure absolute protection against the malarial infection. In the conventional mode of treatment antimalarial drugs, the dose and dosage regimen that is followed at large crops up the contraindicative manifestations, and hence compromising the effective treatment. The emerging trends and new updates in contemporary biological sciences, material sciences, and drug delivery domain have enabled us with the availability of a multitude of mode and modules which could plunge upon the nanotechnology in particular to treat this challenging infection. The nanotechnology-based option may be tuned or customized as per the requirements to mark and target i.e. the infected RBCs, for targeted drug delivery.Graphical abstract

Quality laboratory services are a requisite to guide rational case management of malaria. Using a pre-tested, standardized assessment tool, we assessed laboratory diagnostic capacity in 69 primary, secondary and tertiary health facilities as well as specialized laboratories in five administrative zones in Oromia Regional State, Ethiopia, during February and March 2009. There was marked variability in laboratory diagnostic capacity among the facilities assessed. Of 69 facilities surveyed, 53 provided both comprehensive malaria laboratory diagnosis and outpatient treatment services, five provided malaria microscopy services (referring elsewhere for treatment), and 11 primary care health posts provided rapid diagnostic testing and outpatient malaria treatment. The facilities' median catchment population was 39, 562 and 3581 people for secondary/tertiary and primary health facilities, respectively. Depending on facility type, facilities provided services 24 hrs a day, had inpatient capacity, and access to water and electricity. Facilities were staffed by general practitioners, health officers, nurses or health extension workers. Of the 58 facilities providing laboratory services, 24% of the 159 laboratory staff had received malaria microscopy training in the year prior to this survey, and 72% of the facilities had at least one functional electric binocular microscope. Facilities had variable levels of equipment, materials and biosafety procedures necessary for laboratory diagnosis of malaria. The mean monthly number of malaria blood films processed at secondary/tertiary facilities was 225, with a mean monthly 56 confirmed parasitologically. In primary facilities, the mean monthly number of clinical malaria cases seen was 75, of which 57 were tested by rapid diagnostic test (RDTs). None of the surveyed laboratory facilities had formal quality assurance/quality control protocols for either microscopy or RDTs. This is the first published report on malaria diagnostic capacity in Ethiopia. While our assessment indicated that malaria laboratory diagnosis was available in most facilities surveyed, we observed significant gaps in laboratory services which could significantly impact quality and accessibility of malaria diagnosis, including laboratory infrastructure, equipment, laboratory supplies and human resources.

BackgroundIn 2023, an estimated 36 million pregnancies occurred in malaria endemic sub-Saharan Africa, but only 44% received the WHO recommended ≥ 3 doses of intermittent preventive treatment (IPTp3). Group Antenatal Care (G-ANC) is a service delivery model associated with higher quality of and greater retention in ANC, in which pregnant women are enrolled into groups at their first ANC visit and subsequent care is provided in groups. A cluster-randomized controlled trial was conducted in Atlantique Department, Benin, to assess whether G-ANC improved ANC retention and IPTp3 uptake at community level.MethodsForty purposively selected health facilities (HF) were randomized 1:1 to control (individual ANC) or G-ANC. Cross-sectional household surveys to measure uptake of ANC and IPTp were conducted in each HF catchment area before and after implementation among randomly selected women who had given birth in the previous 12 months. Changes in coverage were assessed using a difference-in-difference approach, adjusting for HF clustering.ResultsAt baseline (N = 1259), coverage of at least 4 ANC visits (ANC4) and IPTp3 was 52.8% and 48.0%, respectively, in the intervention catchment, and 44.9% and 49.4% in the control catchment. Coverage of ANC4 improved in both arms by endline (N = 1280), to 56.7% in the intervention and 46.1% in the control, but the difference in the increase was not significant between arms (p = 0.51). Coverage of IPTp3 increased non-significantly (p = 0.26), to 53.2% (intervention) and 49.7% (control). Overall, only 140 (10.6%) surveyed women reported participating in G-ANC. Participation improved coverage of both ANC4 (65.0% vs 50.5%, p = 0.002; odds ratio (OR) 1.9, 95% CI 1.4–2.5) and IPTp3 (64.0 vs 50.6%, p = 0.004; OR = 1.8, 95% CI 1.2–2.6).ConclusionsG-ANC increased ANC attendance and IPTp3 uptake among women who participated, but participation was limited. Understanding and addressing the barriers to participation is critical if G-ANC is to be used more widely to increase IPTp coverage.Trial Registration: PACTR202405487752509

Malaria is a leading cause of maternal and child mortality in urban Nigeria. Intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp–SP) during pregnancy can prevent malaria but uptake is suboptimal. This cross-sectional study analyzed secondary data on 1159 urban Nigerian women from the 2015 Malaria Indicator Survey using descriptive statistics and logistic regression. The primary outcome was optimal IPTp–SP uptake (≥ 3 doses). 67% of women took any SP during pregnancy but only 39% took ≥ 3 IPTp–SP doses as recommended. Region and wealth index significantly predicted optimal IPTp–SP uptake while education did not. Women from lower-income regions in the urban areas were less likely to receive optimal IPTp–SP. Strategies to increase IPTp–SP uptake in urban Nigeria should target low-income regions and women of lower socioeconomic status. Logistic regression identified actionable factors for improving antenatal malaria prevention. Optimal IPTp–SP uptake remains suboptimal across urban Nigeria, threatening maternal and child health.

This review summarizes accumulating evidence of interactions between HIV and malaria and implications related to prevention and treatment of coinfection. HIV-infected persons are at increased risk for clinical malaria; the risk is greatest when immune suppression is advanced. Adults with advanced HIV may be at risk for failure of malaria treatment, especially with sulfa-based therapies. Malaria is associated with increases in HIV viral load that, while modest, may impact HIV progression or the risk of HIV transmission. Cotrimoxazole prophylaxis greatly reduces the risk of malaria in people with HIV; the risk can be further reduced with antiretroviral treatment and the use of insecticide treated mosquito nets. Increased numbers of doses of intermittent preventive treatment during pregnancy can reduce the risk of placental malaria in women with HIV. Interactions between malaria and HIV have important public health implications. People with HIV should use cotrimoxazole and insecticide treated mosquito nets. Malaria prevention is particularly important for pregnant women with HIV, although more information is needed about the best combination of strategies for prevention. In people with HIV, malaria diagnoses should be confirmed, highly effective drugs should be used for treatment, and possible drug interactions should be considered.

BackgroundIntermittent Preventive Treatment for malaria control in infants (IPTi) consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204].MethodsAfter baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12) or not (n = 12). Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived.ResultsSurvival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P < 0.0001). Over the three years of the study there was a marked improvement in survival in both groups. Between 2001-4 and 2005-7, mortality rates in two-11 month olds fell from 34.1 to 23.6 per 1,000 person-years in intervention areas and from 32.3 to 20.7 in comparison areas. In 2007, divisions implementing IPTi had a 14% (95% CI -12%, 49%) higher mortality rate in two-11 month olds in comparison with non-implementing divisions (P = 0.31).ConclusionThe lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

Malaria is a deadly tropical disease that kills up to 0.6 million people yearly, mostly young children in Africa. Current drug therapies are threatened by drug resistance and the development of novel compounds that are active against drug resistant strains is essential to malarial control and eradication programs. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme for the biosynthesis of pyrimidines required for DNA and RNA synthesis in the parasite. We used a combination of high throughput screening and structure guided medicinal chemistry to optimize a triazolopyrimidine‐based series of DHODH inhibitors resulting in the selection of a clinical candidate for the treatment of malaria. We have shown that DHODH inhibitors have both blood and liver stage anti‐malarial activity, that they have potent activity in both in vitro and in vivo models of malaria and that they are active against a range of clinically drug resistant parasites. A compound called DSM265 was selected from the triazolopyrimidine series for clinical development. DSM265 was shown to have excellent safety during preclinical development. DSM265 has been shown to be a long acting compound with a pharmacokinetic profile that is expected to support single dose treatment or once weekly chemoprevention.Support or Funding InformationThis work was supported by funds from the United States National Institutes of Health grants, U01AI075594 (to MAP, PKR and SAC) and R01AI103947 (to MAP and PKR) and from Medicines for Malaria Venture (MMV).

In sub-Saharan Africa, artemisinin-containing therapies for malaria treatment are regularly co-administered with ART. Currently, dolutegravir-based regimens are recommended as first-line therapy for HIV across most of Africa. To investigate the population pharmacokinetics of dolutegravir during co-administration with artemether/lumefantrine or artesunate/amodiaquine, two commonly used antimalarial therapies. We developed a population pharmacokinetic model of dolutegravir with data from 26 healthy volunteers in two Phase 2 studies with a total of 403 dolutegravir plasma concentrations at steady state. Volunteers received 50 mg of dolutegravir once daily alone or in combination with standard treatment doses of artemether/lumefantrine (80/480 mg) or artesunate/amodiaquine (200/540 mg). A two-compartment model with first-order elimination and transit compartment absorption best described the concentration-time data of dolutegravir. Typical population estimates for clearance, absorption rate constant, central volume, peripheral volume and mean absorption transit time were 0.713 L/h, 1.68 h-1, 13.2 L, 5.73 L and 1.18 h, respectively. Co-administration of artemether/lumefantrine or artesunate/amodiaquine increased dolutegravir clearance by 10.6% (95% CI 4.09%-34.5%) and 26.4% (95% CI 14.3%-51.4%), respectively. Simulations showed that simulated trough concentrations of dolutegravir alone or in combination with artemether/lumefantrine or artesunate/amodiaquine are maintained above the dolutegravir protein-adjusted IC90 of 0.064 mg/L for more than 99% of the individuals. Dolutegravir dose adjustments are not necessary for patients who are taking standard 3 day treatment doses of artemether/lumefantrine or artesunate/amodiaquine.