Predictors of birth weight in pregnant women with malaria: a prospective cohort facility-based study in Webuye-Kenya.

In sub-Saharan Africa, malaria, which remains a major public health burden, has a prevalence of 9 to 28% and malaria in pregnancy is associated with severe adverse outcomes for the mother and her baby. Here, we sought to determine the predictors of birth weight in a cohort of 140 women with malaria in pregnancy, who were recruited at the Webuye County hospital in Western Kenya. All study participants underwent malaria diagnosis through microscopic examination of blood smear samples and were grouped into the malaria-positive and malaria-negative groups. Both groups were followed up beginning at the first antenatal visit (March 2022) until delivery (December 2022) and various data, including demographic, parity, gravidity, socioeconomic, maternal and fetal outcomes were collected. Data analyses were done using SPSS version 27. Chi-square and Fisher's Exact tests were used for bivariate and relative risk analyses at a p-value of ≤0.05 (95%) confidence level. Most of the participants were aged 18-25 years, were primigravidas and married, had secondary school-level education, earned 20-30 thousand Kenya shillings, resided in rural areas, and were in the second trimester. There were 6 (4.6%) cases of low birth weight, 3 (4.5%) in the malaria-negative group and 3 (4.7%) in the malaria-positive group. During pregnancy, 41 (31.5%) were anaemic, 5 (3.8%) were HIV-positive, 5 (3.8%) had preeclampsia, and 2 (1.5%) had gestational diabetes. Our analyses show that confounding factors like anaemia, HIV, pre-eclampsia and gestational diabetes did not influence birthweight (p ≥ 0.923). The malaria-positive and malaria-negative groups did not differ significantly with regard to the low birth weight (relative risk: 0.999, 95% confidence interval: 0.926-1.077). Marital status, gestational age, and area of residence were associated with malaria p ≤ 0.001, ≤ 0.001 and 0.028 respectively. In both groups, 124 of the 140 deliveries had normal birth weights and of these 63 (95.4%, n = 70) were in the malaria-negative group, whereas 61 (95.3%, n = 70) belonged to the malaria-positive group.

Improving Access to Safe Water in Rural Schools of Kenya: Qualitative Multisectoral Insights.

BACKGROUND: Comprehensive strategies in water, sanitation, and appropriate hygiene behaviors can improve school enrolment and improve gender parity disparities. Lack of safe drinking water negatively impacts the social capital of people, especially school-going children in rural areas. In this study, we systematically evaluated and documented evidence on the barriers and facilitators in the access and adoption of safe water practices in rural schools in Laikipia County, Kenya. METHODS: An ethnographic formative, collaborative implementation research design was used in an iterative and participatory process to evaluate community, socio-economic, and health system-related factors affecting water, hygiene, and sanitation strategies. Qualitative data was collected using key informant interviews (n=5) and focus groups (n=3) from various multisectoral participants. Directed content analysis was used to develop codes, categories, and themes from textual data. Data was organized according to the Promoting Action on Research Implementation in Health Services framework. RESULTS: The findings were classified and described under three key elements: context, evidence, and facilitation. Contextual elements showed an association of diarrhea outbreaks with unsafe hygiene practices compounded by water scarcity. The evidence elements were indicative of the applicability of water backpacks in strengthening handwashing, storage, and transport of water. Facilitation elements indicated evidence of gaps in synergy between the school health and public health systems, necessitating multisectoral collaboration and social capital capacity building. CONCLUSION: The national and county governments play an imperative role in ensuring access and continuous supply of safe drinking water in schools. This is fundamental in efforts towards reducing social inequalities of health among school-going children and building their social capital. Participatory, collaborative, multisectoral interventions and decision-making are crucial, leveraging on creating local ownership, in meeting the water consumption needs of children and communities in water-scarce regions.

The impact of measures to curb COVID-19 on patient attendance at 10 hospitals in Machakos County, Kenya.

BACKGROUND: The COVID-19 pandemic has resulted in both direct and indirect impacts on patients and population health. To better understand the impact of the measures put in place by the Kenyan government on health care provision, this project sought to document and quantify the impact of the restriction measures on patients' attendance in Machakos County. METHODS: Hospital attendance at 10 public hospitals were obtained including Machakos Level 5 Hospital (the county referral facility) and one health facility from each of the 9 Sub-counties of Machakos County. Data on outpatient and inpatient attendance from November 2019 to May 2020 were obtained and compared with a similar calendar period from the previous year. Key informant interviews (KIIs), focused group discussions (FGDs) and in-depth interviews were conducted with the hospital management personnel (n = 46), as well as with the patients (n = 453) who missed scheduled clinic appointments at Machakos Level 5 Hospital to understand the reasons behind the drop in attendance numbers. RESULTS: Overall, there was a decline in the number of patient attendances compared to the prior calendar period. Outpatient attendance reduced by 24.7% in April 2020 (n = 39 704) compared with April 2019 (n = 52 731). Inpatient attendance reduced by 13.7% in April 2020 (n = 3298) compared with April 2019 (n = 2845). Declines in patient attendance were observed in all hospitals that had inpatient services. A great decline in attendance was noted among larger hospitals that run specialty clinics, which were suspended mid-March 2020 when the first case of COVID-19 was announced. Some increase in attendance was noted in May when most clinics resumed operations. Most hospital management staff highlighted the closure of clinics as the main reason for reduced attendance while patients added that they also feared contracting COVID-19 at the hospital and the stigma they would face should they be quarantined. CONCLUSIONS: The findings from this study provide evidence that the COVID-19 pandemic outbreak and measures put in place by the government to curb its spread disrupted the provision of health services in Machakos County. Efforts to minimize adverse impacts of indirect impacts on access to health care and preventative services to counter increased morbidity and mortality require attention throughout the pandemic.

Leveraging technology for health services continuity in times of COVID-19 pandemic: Patient follow-up, and mitigation of worse patient outcomes.

BACKGROUND: Since the outbreak of the COVID-19 pandemic in Wuhan, China, which has now spread globally, the health systems continue to face challenges in the provision of health care, there is a risk of exposure for both the physicians and the patients. While there is significant progress in the adoption of technology in health care. This study sought to examine the adverse effects of the measures put in place by the government to curb the spread of COVID-19 and come up with an intervention to prevent worse outcomes for chronic conditions. METHODS: Booking registers for four specialty clinics in Machakos Level 5 Hospital were reviewed to identify patients who missed clinic appointments for follow-up. An automated data collection tool (ODK-collect) was used for data collection. COVID-19 Machakos App was developed to facilitate follow-up and referral of patients to the nearest facilities, capturing and posting of information in real-time to a central database. The mobile App also facilitated the tracking of patients and aided doctors to give feedback on whether the patients reported to the referred facilities. The doctors were also able to capture doctors' notes on the patients' status while ensuring the confidentiality and privacy of the patients. An interactive dashboard was developed to generate analytics reports and summaries to monitor clinic attendance and trends in the provision of health care during the pandemic period. RESULTS: Register data showed 977 (81.5%) out of a total of 1199 patients had missed their scheduled appointments. Among the 977, 746 (76%) were residents of Machakos County and qualified for follow-up. Missed appointments varied by clinic: Cancer Clinic 12 (1.6) %), Diabetes Clinic 212 (28.4%), Hypertension 293 (39.3%), and Paediatrics Clinic 229 (30.7%). Contact was made and follow-up was attempted for 746 patients, of which 453 patients (60.7%) were successful. The follow-up distribution of the 453 patients varied by the clinic as follows: Cancer Clinic 10, Diabetes Clinic 146, Hypertension 185, and Paediatrics Clinic 112. During the follow-up process, 331 patients from diabetes and hypertension clinics were requested to choose a preferred or nearby facility to be referred to. 191 (58%) patients chose Machakos Level 5 Hospital as their preferred facility and 137 (41%) patients chose to be referred to level 3 or 4 hospitals within the County. Three deaths were reported from the medical (Hypertension) clinic. Through the developed App, a total, 82 (60%) patients out of the 137 were reviewed at the referral facilities jointly with a specialist at Machakos Level 5 Hospital. For the duration of the study, some patients reported worse conditions by the time of review after missing scheduled appointments. CONCLUSIONS: This intervention demonstrated that mobile phone technology could be leveraged to provide specialty treatment services remotely to mitigate against worse patient outcomes. The study reveals that there is a dire need to integrate technological interventions in the provision of health care services to ensure continuity.

Chemical Synthesis, Efficacy, and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds.

Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosquitoes. According to the WHO report of 2015, there were 214 million cases of malaria with 438,000 deaths worldwide. Ninety percent of world's malaria cases occur in Africa, where the disease is recognized as a serious impediment to economic and social development. Despite advancement in malaria research, the disease continues to be a global problem, especially in developing countries. Currently, there is no effective vaccine for malaria control. In addition, although there are effective drugs for treatment of malaria, this could be lost to the drug resistance in different Plasmodium species. The most lethal form is caused by P. falciparum which has developed resistance to many chemotherapeutic agents and possibly to the current drugs of choice. Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared toward combating the disease. Covalent bitherapy is a rational and logical way of drug design which entails joining a couple of molecules with individual intrinsic action into a unique agent, hence packaging dual activity into one hybrid. This suggests the need to develop new antimalarial drugs that are effective against malaria parasites based on the new mode of action, molecular targets, and chemical structures. In silico studies have shown that sarcosine is able to bind to unique plasmodia proteins (P. falciparum ATCase), whereas aniline can be a ligand to target protein (enoyl acyl carrier protein reductase), hence suppressing the progression of the disease. The main objective of this study was to synthesize and determine the efficacy and safety of antiplasmodial hybrid drug comprising the sarcosine and aniline derivative for management of plasmodial infections. The hybrid drug was synthesized by adding thionyl chloride to sarcosine to form acyl chloride which was then added to aniline to form sarcosine-aniline hybrid molecule. The IC50 of sarcosine-aniline hybrid was 44.80 ± 4.70 ng/ml compared with that of aniline derivative which was 22.86 ± 1.26 ng/ml. The IC50 of control drugs was 2.63 ± 0.38 ng/ml and 5.69 ± 0.39 ng/ml for artesunate and chloroquine, respectively. There was a significant difference between IC50 of sarcosine-aniline hybrid and aniline derivative (p < 0.05). There was also a significant difference between sarcosine-aniline hybrid and standard drugs used to treat malaria including artesunate and chloroquine (p < 0.05). The ED50 of sarcosine-aniline hybrid drug was 6.49 mg/kg compared with that of aniline derivative which was 3.61 mg/kg. The ED50 of control drugs was 3.56 mg/kg, 2.94 mg/kg, and 1.78 mg/kg for artesunate-aniline hybrid, artesunate, and chloroquine, respectively. There was a significant difference (p < 0.05) between ED50 of sarcosine-aniline hybrid and both controls such as aniline derivative, artesunate, artesunate-aniline hybrid, and chloroquine. Cytotoxicity results revealed that sarcosine-aniline hybrid was safe to vero cells with a CC50 of 50.18 ± 3.53 µg/ml. Sarcosine-aniline hybrid was significantly less toxic compared with artesunate, chloroquine, and doxorubicin. Sarcosine-aniline hybrid was efficacious and safe to mice. Therefore, covalent bitherapy should be used in drug development for drug resistance mitigation.

Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model.

BACKGROUND: The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. The study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed 'covalent bitherapy' could improve the curative outcomes in cerebral malaria infections. METHODS: Human cerebral malaria rodent model, the C57BL/6 male mice were infected intraperitoneally (ip) with Plasmodium berghei ANKA and intravenously (iv) treated with the trioxaquine from day 8 post-infection (pi) at 12.5 and 25 mg/kg, respectively, twice a day for 3 days. Treatments with the trioxaquine precursors (artesunate and 4,7-dichloroquine), and quinine were also included as controls. In vivo safety evaluation for the trioxaquine was done according to Organization for Economic Co-operation and Development (OECD) guidelines 423, where female Swiss albino mice were orally administered with either 300 or 2000 mg/kg of the trioxaquine and monitored for signs of severity, and or mortality for 14 days post-treatment. RESULTS: The trioxaquine showed a potent and a rapid antiplasmodial activity with 80% parasite clearance in the first 24 h for the two dosages used. Long-term parasitaemia monitoring showed a total parasite clearance as the treated mice survived beyond 60 days post-treatment, with no recrudescence observed. Artesunate treated mice showed recrudescence 8 days post-treatment, with all mice in this group succumbing to the infection. Also, 4,7-dichloroquinoline and quinine did not show any significant parasitaemia suppression in the first 24 h post-treatment, with the animals succumbing to the infection. CONCLUSION: Covalent bitherapy proves to be a viable source of urgently needed new anti-malarials for management of cerebral malaria, and this polypharmacology approach could be a potential strategy to protect artesunate from parasite resistance and in potentially improving clinical outcomes in severe forms of malaria infections.

Electrochemical deallylation of alpha-allyl cyclic amines and synthesis of optically active quaternary cyclic amino acids.

Electrochemical oxidation of alpha-allylated and alpha-benzylated N-acylated cyclic amines by using a graphite anode easily affords the corresponding alpha-methoxylated products with up to 76 % yield. Ease of oxidation was affected by the type of electrode, the size of cyclic amine, and the nature of the protecting group. This method was successfully applied to the synthesis of optically active N-acylated alpha-alkyl-alpha-amino acid esters with up to 99 % ee.

Anti-parasitic activity and cytotoxicity of selected medicinal plants from Kenya.

Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmaniasis, using herbal drugs. The efficacy, dosage, safety and active principles of most of the herbal preparations are not known. Extracts from 6 selected plant species, used as medicinal plants by indigenous local communities in Kenya, were screened for in vitro anti-plasmodial and anti-leishmanial activity, against 2 laboratory-adapted Plasmodium falciparum isolates (D6, CQ-sensitive and W2, CQ-resistant) and Leishmania major (IDU/KE/83=NLB-144 strain), respectively. The methanol extract of Suregada zanzibariensis leaves exhibited good anti-plasmodial activity (IC(50) 4.66+/-0.22 and 1.82+/-0.07 microg/ml for D6 and W2, respectively). Similarly, the methanol extracts of Albizia coriaria (IC(50) 37.83+/-2.11 microg/ml for D6) and Aspergillus racemosus (32.63+/-2.68 and 33.95+/-2.05 microg/ml for D6 and W2, respectively) had moderate anti-plasmodial activity. Acacia tortilis (IC(50) 85.73+/-3.36 microg/ml for W2) and Albizia coriaria (IC(50) 71.17+/-3.58 microg/ml for W2) methanol extracts and Aloe nyeriensis var kedongensis (IC(50) 87.70+/-2.98 and 67.84+/-2.12 microg/ml for D6 and W2, respectively) water extract exhibited mild anti-plasmodial activity. The rest of the extracts did not exhibit any anti-plasmodial activity. Although the leishmanicidal activity of extracts were lower than for pentosam (80%), reasonable activity was observed for Aloe nyeriensis methanol (68.4+/-6.3%), Albizia coriara water (66.7+/-5.0%), Maytenus putterlickoides methanol (60.0+/-6.23%), Asparagus racemosus methanol and water (58.3+/-8.22 and 56.8+/-6.58%, respectively), Aloe nyeriensis water (53.3+/-5.1%) and Acacia tortilis water (52.9+/-6.55%) extracts at 1000 microg/ml. Leishmania major infected macrophages treated with methanol extracts of Suregada zanzibariensis and Aloe nyeriensis var kedongensis and pentostam had infection rates of 28+/-2.11, 30+/-1.22 and 40+/-3.69%, respectively at 1000 microg/ml, indicating better anti-leishmanial activity for the extracts. The methanol extract of Albizia coriara (44.0+/-3.69%) and aqueous extracts of Asparagus racemosus (42+/-3.84%) and Acacia tortilis (44+/-5.59%) had similar activity to pentosam. Multiplication indices for Leishmania major amastigotes treated with methanol extracts of Albizia coriaria, Suregada zanzibariensis and Aloe nyeriensis var kedongensis, aqueous extract of Acacia tortilis and pentosam were 28.5+/-1.43, 29.4+/-2.15, 31.1+/-2.22, 35.9+/-3.49 and 44.0+/-3.27%, respectively, at 1000 microg/ml, confirming better anti-leishmanial activity for the extracts. Aqueous extracts of Aloe nyeriensis (46.7+/-3.28%) and Albizia coriaria (47.5+/-3.21%) had similar activity level to pentosam. The plant extracts have better inhibitory activity while pentosam has better leishmanicidal activity. All extracts exhibited very low cytotoxicity (CC(50) > 500 microg/ml) against human embryonic lung fibroblast (HELF) cells. The investigations demonstrated the efficacy and safety of some extracts of plants that are used by rural indigenous communities for the treatment of parasitic diseases.

Tigliane diterpenoids from the stem bark of Neoboutonia macrocalyx.

Neoboutonia macrocalyx is a plant used by traditional healers among the Meru community in Kenya. Chromatographic fractionation of the petroleum ether and dichloromethane extracts of this plant yielded one known (1) and three new tigliane-type diterpenoids (2-4). The chemical structures of the isolated compounds were established through spectroscopic data interpretation.