Measuring protective efficacy and quantifying the impact of drug resistance: A novel malaria chemoprevention trial design and methodology.

BACKGROUND: Recently revised WHO guidelines on malaria chemoprevention have opened the door to more tailored implementation. Countries face choices on whether to replace old drugs, target additional age groups, and adapt delivery schedules according to local drug resistance levels and malaria transmission patterns. Regular routine assessment of protective efficacy of chemoprevention is key. Here, we apply a novel modelling approach to aid the design and analysis of chemoprevention trials and generate measures of protection that can be applied across a range of transmission settings. METHODS AND FINDINGS: We developed a model of genotype-specific drug protection, which accounts for underlying risk of infection and circulating genotypes. Using a Bayesian framework, we fitted the model to multiple simulated scenarios to explore variations in study design, setting, and participant characteristics. We find that a placebo or control group with no drug protection is valuable but not always feasible. An alternative approach is a single-arm trial with an extended follow-up (>42 days), which allows measurement of the underlying infection risk after drug protection wanes, as long as transmission is relatively constant. We show that the currently recommended 28-day follow-up in a single-arm trial results in low precision of estimated 30-day chemoprevention efficacy and low power in determining genotype differences of 12 days in the duration of protection (power = 1.4%). Extending follow-up to 42 days increased precision and power (71.5%) in settings with constant transmission over this time period. However, in settings of unstable transmission, protective efficacy in a single-arm trial was overestimated by 24.3% if recruitment occurred during increasing transmission and underestimated by 15.8% when recruitment occurred during declining transmission. Protective efficacy was estimated with greater precision in high transmission settings, and power to detect differences by resistance genotype was lower in scenarios where the resistant genotype was either rare or too common. CONCLUSIONS: These findings have important implications for the current guidelines on chemoprevention efficacy studies and will be valuable for informing where these studies should be optimally placed. The results underscore the need for a comparator group in seasonal settings and provide evidence that the extension of follow-up in single-arm trials improves the accuracy of measures of protective efficacy in settings with more stable transmission. Extension of follow-up may pose logistical challenges to trial feasibility and associated costs. However, these studies may not need to be repeated multiple times, as the estimates of drug protection against different genotypes can be applied to different settings by adjusting for transmission intensity and frequency of resistance.

First detection of Rift Valley fever virus antibodies in non-human primates in Cameroon.

We tested for Rift Valley fever virus (RVFV) from at least 15 species of non-human primates. RVFV IgG/IgM antibodies were detected in 3.7% (2 out of 53) of chimpanzees (Pan troglodytes) and in 1.4% (1 out of 72) of unidentified non-human primate species. This study was the first investigation of RVFV in monkeys in Cameroon.

Contemporary epidemiological data of Rift Valley fever virus in humans, mosquitoes and other animal species in Africa: A systematic review and meta-analysis.

Rift Valley fever (RVF) is a severe zoonotic mosquito-borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta-analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta-analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random-effects model. Subgroup analysis and sensitivity analysis were performed, and the I2 -statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0-52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2-9.6] in humans and 9.3% [95% CI = 8.1-10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health.

MCP-1-2518 (A>G) polymorphism and asthma risk: a pilot case-control study in Cameroon.

Introduction: there is little data on the genetic determinants of asthma in Cameroon and sub-Saharan Africa, yet the involvement of genetics in the pathogenesis of this disease has been reported in the literature for several years. This study aims to investigate the possible role of MCP-1 2518 for the risk of asthma in Cameroonians. Methods: we performed a case-control study on 30 volunteers suffering from asthma, matched by aged and sex to 30 healthy subjects. We determine the polymorphism of MCP-1 2518 using restriction fragment length polymorphism following Polymerase Chain Reaction (RFLP-PCR). Fisher exact test was used to compare proportions, with a threshold of significance set at 0.05. Results: the average age of cases was 21±10 years with 17 (56.7%) females. The distribution of the MCP-1-2518 (A>G) gene polymorphism in people with asthma was as follows: 3 for AA, 5 for GG, and 22 for AG. The minor G allele was predominant (90%) in people with asthma. It was significantly associated with asthma whether the genotype was heterozygous AG or homozygous GG (p<0.01). Conclusion: MCP-1-2518 (A>G) shows an association with asthma in our sample. Future larger studies evaluating several polymorphisms are needed to describe the genetic determinants of asthma in Cameroon and sub-Saharan Africa.

Evolution of Plasmodium falciparum antimalarial drug resistance markers post-adoption of artemisinin-based combination therapies in Yaounde, Cameroon.

OBJECTIVES: This study aimed to investigate the evolution of Plasmodium falciparum antimalarial drug resistance markers by comparing the pre- and post-adoption of artemisinin-based combination therapies (ACTs) in Yaounde, Cameroon. METHODS: The molecular characterization of known antimalarial drug resistance markers (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and Pfk13) in P. falciparum-positive samples collected in 2014 and 2019-2020 was achieved using nested polymerase chain reaction, followed by targeted amplicon deep sequencing on the Illumina MiSeq platform. Data derived were compared with those published during the pre-ACT adoption period from 2004 to 2006. RESULTS: A high prevalence of Pfmdr1 184F, Pfdhfr 51I/59R/108N, and Pfdhps 437G mutant alleles was observed during the post-ACT adoption period. The Pfcrt 76T and Pfmdr1 86Y mutant alleles significantly declined between 2004 and 2020 (P <0.0001). Conversely, the resistance markers to antifolates, Pfdhfr 51I/59R/108N and Pfdhps 437G, significantly increased during the same study period (P <0.0001). We identified nine mutations in the propeller domains of Pfk13; although they were all present in single parasite isolates, none of them are known to confer artemisinin resistance. CONCLUSION: This study documented a near-complete reversion to sensitive parasites for markers conferring resistance to the 4-aminoquinolines and arylamino alcohols in Yaounde. In contrast, the Pfdhfr mutations associated with pyrimethamine resistance are moving toward saturation.

Maternal Socio-Demographic Factors and Mother-to-Child Transmission of HIV in the North Region of Cameroon.

Background and Objective: Socio-demographic factors are important risk factors for HIV infection. Maternal socio-demographic factors associated with HIV transmission from mother to child are not well elucidated to our knowledge. This study aimed to assess the maternal socio-demographic factors associated with HIV vertical transmission. Methods: A matched case-control study was conducted among children under 15 years of age born to HIV-infected mothers; using a structured questionnaire. The study was conducted in four health facilities in the North Region of Cameroon from July 2015 to October 2016. HIV- infected children were the cases, and HIV-uninfected children were the controls. One case was matched to nearly 4 controls according to age and sex. A total of 113 HIV-infected mothers of children under 15 years of age were purposively enrolled in the study. A questionnaire was administered to mothers and socio-demographic characteristics were collected. Blood samples were collected from the mother and her child for the determination or confirmation of HIV status. Univariate and multiple logistic regressions were used to assess associations between socio-demographic variables and HIV transmission from mother to child. Results: A total of 113 HIV-infected mothers and 113 children under 15 years of age were enrolled in this study. The majority of the mothers were between the age ranges of 25 years to 34 years. Of the 113 HIV-infected mothers, 69 (61%) were Muslims, 33 (32.1%) were not educated, 88 (77.8%) were unemployed, 80 (70.9%) were married, out of which 49 (61.6%) were engaged in a monogamous union. Of the 113 children (49.6%) were female, 25 (22.1%) were HIV-infected and 88 (77.9%) were HIV-exposed uninfected. At the univariate level, mothers who achieved a primary level of education were less likely to transmit HIV to infants compared to uneducated mothers [OR=0.28; CI (0.08-0.95); p=0.04]; and widows had a higher likelihood of HIV transmission to infants compared to married mothers [OR=4.65; CI (1.26-17.20); p=0.02]. Using multiple logistic regression, the maternal primary education level [aOR=0.32; CI (0.08-0.90); p=0.03] and widowerhood [aOR=7.05; CI (1.49-33.24); p=0.01] remained highly associated with the likelihood of HIV transmission to infants. Conclusion and Global Health Implications: Uneducated mothers and widows had a higher likelihood of mother-to-child transmission of HIV. Our findings should prompt reinforcement of prevention strategies targeting uneducated women and widows.

Allelic frequencies of mutants of the Plasmodium falciparum, quinoline and folate metabolizing genes in the west region of Cameroon.

The emergence and spread of Plasmodium falciparum (P.f) drug resistance is still a major concern in Sub-Saharan Africa and warrants that its evolution be monitored continuously. The present study aimed at determining the distribution of key P.f drug resistance-mediating alleles in circulating malaria parasites in the West region of Cameroon. A cross sectional hospital-based study was conducted in Dschang and Ngounso in the West region of Cameroon. The Pfcrt, Pfmdr1, and the Pfdhps genes were amplified through nested PCR in 208 malaria-infected samples of the 301 febrile outpatients enrolled. The presence or absence of mutations in the K76T, N86Y, A437G and A581G codons of these P.f. genes respectively were determined through restriction digestion analysis. The proportion of different alleles were estimated as percentages and compared between two study sites using the Chi square test. A p value <0.05 was considered significant. A high prevalence (75.6%) of the 437G allele was observed. It was significantly different between Dschang and Ngounso (62% vs. 89.2%, X2 = 19.6, P = 0.00005). Equally observed was a 19.2% (95%CI: 13.3-25.6) of the dhps-581G mutant allele. Furthermore, we observed the Pfcrt-76T, Pfmdr1-N86 mutations in 73.0% (67.5-79.7) and 87.2% (83.2-91.9), and 3.0% (0.0-9.6) and 12.8% was observed for the Pfcrt-K76T and Pfmdr1-N86Y respectively. When biallelic haplotypes were constructed from alleles of the three genes, same pattern was seen. Overall, 73% and 87% of circulating P. falciparum isolates carried wild type alleles at Pfmdr1-N86Y and Pfcrt-K76T. On the other hand, we found more parasites with mutant alleles at dhps (437G and 581G) loci which may reflect possible drug-related selection of this mutant in the parasite population. Continuous monitoring of these mutations is recommended to pre-empt a loss in sulphadoxine-pyrimethamine efficacy in malaria chemoprevention programs.

Noninvasive Approach of Plasmodium falciparum Molecular Detection for Malaria Surveillance in Malaria Endemic Areas in Cameroon.

Background: Accurate, cost-effective, and noninvasive alternative molecular methods are needed for detecting low malaria parasitemia. The currently-used nested polymerase chain reaction (nPCR) requires blood as well as skilled personnel in order to minimise the risk of bloodborne disease transmission. Therefore, this study is aimed at assessing the accuracy of a noninvasive and more affordable malaria diagnosis with saliva using the loop-mediated isothermal amplification (LAMP) technique. Methods: A cross-sectional study was conducted in the Centre and Southwest regions of Cameroon. Matched blood and saliva samples collected from symptomatic and asymptomatic participants were tested for malaria using rapid diagnostic tests, microscopy, PCR, and LAMP. Statistics were performed using R studio software at 95% confidence interval. Results: A total of 100 participants (65% symptomatic and 35% asymptomatic) aged between 1 and 74 years with a balanced gender distribution ratio of 1.08 were included in our study. The prevalence of malaria was 61%, 57%, 59%, 42%, 35%, 17%, and 16% for blood-RDT, blood-PCR, blood-LAMP, blood-RT-LAMP, saliva-PCR, saliva-RT-LAMP, and saliva-LAMP, respectively. Both saliva and blood showed a sensitivity of 43.90% and respective specificities of 68.75% and 57.62%. When using RT-LAMP, sensitivities of 49.38% and 48.21% and specificities of 94.11% and 66.67% were recorded for saliva and blood, respectively. Sensitivities of 70.23% and 73.49% and specificities of 62.5% and 76.47% were recorded, respectively, for saliva-LAMP and saliva-RT-LAMP when compared to saliva-PCR as the gold standard. Saliva-LAMP and saliva-RT-LAMP had a fair agreement (к = 0.221 and 0.352, respectively) with saliva-PCR. Homemade LAMP and RT-LAMP technologies match the WHO recommendations and after proper validation in a larger sample size, could serve for malaria diagnosis in developing countries.

Motivators and demotivators to accessing malaria in pregnancy interventions in sub-Saharan Africa: a meta-ethnographic review.

BACKGROUND: Despite the introduction of efficacious interventions for malaria control, sub-Saharan Africa continues to bear the highest burden of malaria and its associated effects on vulnerable populations, such as pregnant women and children. This meta-ethnographic review contributes to literature on malaria in pregnancy interventions in sub-Saharan Africa by offering insights into the multiple factors that motivate or demotivate women from accessing MiP interventions. METHODS: A meta-ethnographic approach was used for the synthesis. Original qualitative research articles published from 2010 to November 2021 in English in sub-Saharan Africa were searched for. Articles focusing on WHO's recommended interventions such as intermittent preventive treatment with sulfadoxine-pyrimethamine, long-lasting insecticidal nets and testing and treatment of Malaria in Pregnancy (MiP) were included. Selected articles were uploaded into Nvivo 11 for thematic coding and synthesis. RESULTS: Twenty-seven original qualitative research articles were included in the analysis. Main factors motivating uptake of MiP interventions were: (1) well organized ANC, positive attitudes of health workers and availability of MiP services; (2) Women's knowledge of the effects of malaria in pregnancy, previous experience of accessing responsive ANC; (3) financial resources and encouragement from partners, relatives and friends and (4) favourable weather condition and nearness to a health facility. Factors that demotivated women from using MiP services were: (1) stock-outs, ANC charges and health providers failure to provide women with ample education on the need for MiP care; (2) perception of not being at risk and the culture of self-medication; (3) fear of being bewitched if pregnancy was noticed early, women's lack of decision-making power and dependence on traditional remedies and (4) warm weather, long distances to health facilities and the style of construction of houses making it difficult to hang LLINs. CONCLUSIONS: Health system gaps need to be strengthened in order to ensure that MiP interventions become accessible to women. Additionally, health managers need to involve communities in planning, designing and implementing malaria interventions for pregnant women. It is important that the health system engage extensively with communities to facilitate pregnant women and communities understanding of MiP interventions and the need to support pregnant women to access them.

Serological evidence of the circulation of the Rift Valley fever virus in sheep and goats slaughtered in Yaoundé, Cameroon.

BACKGROUND: Rift Valley fever (RVF) is an emerging mosquito-borne haemorrhagic fever disease capable of causing severe outbreaks with high mortality and morbidity in human, livestock, and wildlife species, particularly in Africa. The onset of the disease in humans is often preceded by epizootic circulation in animals. Therefore, this study was conducted to investigate the seroprevalence of Rift Valley fever virus (RVFV) infection in animals slaughtered in the "Marché huitième" slaughterhouse in Yaoundé, Cameroon. METHODS: A cross-sectional study was conducted at the "Marché huitième" slaughterhouse in Yaoundé, Centre region of Cameroon in March 2020. Blood samples of two species of small ruminants (sheep and goat) were collected and processed. Serum was analysed for detection of RVFV IgG and IgM using commercial ELISA tests. RESULTS: Of the 191 ruminants tested, RVFV IgG antibodies were positive in 10 (5.2%). Regarding categorization of the population based on the species and gender, sheep and female animal had the highest seroprevalence of 6.4% (3/47) and 7.0% (8/115), respectively. All sera from IgG antibodies-positive samples were negative to IgM antibodies. CONCLUSION: This study provides evidence of the circulation of RVFV in small ruminants sold and slaughtered at the "Marché huitième" slaughterhouse in Yaoundé and highlights the need to develop a surveillance system for this virus encompassing humans, livestock, wildlife, and vectors in Cameroon.

A qualitative assessment of the health systems factors influencing the prevention of malaria in pregnancy using intermittent preventive treatment and insecticide-treated nets in Ghana.

BACKGROUND: Ghana has adopted and implemented intermittent preventive treatment using sulfadoxine-pyrimethamine (IPTp-SP) and insecticide-treated nets (ITNs) in an antenatal care (ANC) context to prevent malaria among pregnant women. However, the increased ANC attendance and its frequency facilitated by a free maternal health care policy in Ghana does not correspond with the uptake of IPTp-SP and ITN use among pregnant women. This study sought to elucidate the contextual health system factors influencing the delivery of IPTp-SP and ITN from a related quantitative study conducted in Ghana. METHODS: This is the qualitative section of a mixed-methods study design, where audio recorded key informant interviews (KIIs) were conducted with health workers from across health facilities, districts, regional and national health directorates. The KIIs elicited information on health worker knowledge, perceptions, and rationale for the delivery practices of IPTp-SP and ITN revealed in the quantitative findings. The interviews were transcribed and imported into NVivo for analysis. Using the World Health Organization (WHO) Health Systems Framework as the theoretical basis, thematic analysis was conducted under broad themes of the building blocks. Findings are presented in narrative quotes, with a mindmap used to summarize the various health system factors and their interrelated relationship influencing the delivery of IPTp-SP and ITN. RESULTS: Health system factors identified included health staff untrained on malaria delivery directives due to an ineffective trainer of trainer (ToT) system. Additionally, health worker confusion on when to commence SP (at quickening or ≥ 16 weeks) was found to result in delayed start of SP. Stock-outs in facilities due to procurement delays at the national level resulted in missed opportunities to deliver SP to eligible pregnant women at the ANC. Similarly, ITN stock outs led to eligible pregnant women not receiving one at ANC clinics. CONCLUSION: Poor health worker knowledge on policy directives, a consequence of ineffective training strategy led to delayed delivery of IPTp-SP to eligible pregnant women. Supply chain management challenges related to stock of SP and ITN resulted in missed opportunities to deliver the interventions to pregnant women attending ANC.

Procalcitonin levels in children affected by severe malaria compared to those with uncomplicated malaria in the absence of bacterial infection: a cross-sectional study.

BACKGROUND: Procalcitonin is an inflammatory marker strongly associated with the presence of bacterial infection. It has been considered raised in severe malaria infection as opposed to uncomplicated malaria. There are suggestions that it may be raised only when there is concomitant unnoticeable bacterial infection during a malaria crisis. We aimed to assess the difference in plasma procalcitonin levels between children affected by severe and uncomplicated malaria. METHODS: We assessed plasma procalcitonin levels in 83 children diagnosed with malaria with no clinical and biological evidence of concomitant bacterial infection. Severity of malaria was established using WHO guidelines. Procalcitonin was determined using the ELISA method. Non-parametric Mann-Whitney U test was used to compare medians across the 2 groups. Statistical significance was set for all p values < 0.05. RESULTS: Of the 83 participants, 28 had uncomplicated malaria, and 55 had severe malaria. PCT levels were obtained in 24 and 40 subjects of each group, respectively, and were similar in both groups; [2.76 (2.52-2.93) vs 2.74 (2.52-2.98) ng/ml, p = 0.916]. The parasite density was lower in the uncomplicated malaria group than in the severe malaria group, but not statistically significant; [22,192 (9110-44 654) vs 31 684 (13 960-73 500) parasites/µl, p = 0.178]. There was no correlation between the parasite density in the general study population and PCT levels (r = 0.072, p = 0.572). CONCLUSION: In the absence of overt bacterial infection, procalcitonin levels are not different between children affected with uncomplicated malaria and those with severe malaria. Therefore, bacterial infection should be thoroughly checked for in children with raised serum procalcitonin diagnosed with severe malaria.

Current status of 4-aminoquinoline resistance markers 18 years after cessation of chloroquine use for the treatment of uncomplicated falciparum malaria in the littoral coastline region of Cameroon.

The onset and rapid spread of chloroquine resistance and the introduction of amodiaquine for the treatment of uncomplicated malaria in Cameroon have influenced the proportion of Plasmodium falciparum sensitive and resistant alleles related to 4-aminoquinoline drugs. This study was undertaken to determine the prevalence of resistance markers to antimalarial 4-aminoquinolines in Douala in the Littoral Region, and Buea in the South West Region in June 2020. Dry blood spots were prepared from malaria microscopy positive cases and used for parasite DNA extraction by chelex-100 method. Plasmodium species identification was carried out by PCR amplification/agarose gel electrophoresis of 18srRNA. The Pfcrt and Pfmdr1 genes were amplified by PCR followed by restriction digestion. The prevalence of single nucleotide polymorphisms (SNPs) was compared between study sites and with previous studies carried out between 2003-2005 and 2009-2011 using the Chi square test. The results showed that Plasmodium falciparum was the dominant species occurring as mono-infections (84.6%). The wild type K76 allele of the Pfcrt gene was found in 74.9% of isolates while the wild N86, Y184 and D1246 alleles of the Pfmdr1 gene were found respectively in 87.2%, 89.6% and 100% of field isolates. The results showed a significant reduction in the mutant alleles compared to results obtained in 2003-2005 and 2009-2013. The KNYD haplotype was observed to be the most prevalent. The results indicated that there is a gradual erosion of the mutant Pfcrt and Pfmdr1 genotype and a gradual return to the sensitive P. falciparum genotype in Cameroon.

Relation between haptoglobin polymorphism and oxidative stress status, lipid profile, and cardiovascular risk in sickle cell anemia patients.

OBJECTIVE: The haptoglobin (Hp) gene located on chromosome 16q22 exhibits a polymorphism that can impact its capacity to inhibit the deleterious oxidative activity of free hemoglobin. We aimed to determine the influence of Hp polymorphism on oxidative stress, lipid profile, and cardiovascular risk in Cameroonian sickle cell anemia patients (SCA patients). METHOD: The Hp genotypes of 102 SCA patients (SS), 60 healthy individuals (AA), and 55 subjects with sickle cell trait (AS) were determined by allele-specific PCR, and the blood parameters were assessed using standard methods. RESULTS: Hp2-2 genotype was significantly (P < .05) present in SS (54%) than in AS (42%) and AA (38%). Levels of catalase and cell reactive protein were higher, while levels of total antioxidant capacity, triglycerides, low-density lipoprotein cholestetol, blood pressure, Framingham score, and body mass index were lower in the SCA patients. These parameters appeared to be unrelated to the haptoglobin genotypes. SCA patients with Hp1-1 genotype presented a higher oxidative stress index (0.53 ± 0.31) than those with Hp2-1 (0.33 ± 0.18). Lipid profile and cardiovascular risk were not significantly different between various Hp genotypes in SCA patients. CONCLUSION: Haptoglobin polymorphism did not affect lipid profile, cardiovascular risk, and oxidative stress status of SCA patients. Nevertheless, SCA patients with Hp1-1 genotype tended to be more prone to oxidative stress than those with Hp2-1.

Effectiveness and safety of artesunate-amodiaquine versus artemether-lumefantrine for home-based treatment of uncomplicated Plasmodium falciparum malaria among children 6-120 months in Yaoundé, Cameroon: a randomized trial.

BACKGROUND: Many studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in Cameroon. There is paucity of data to support their continuous use in home-based treatment of uncomplicated Plasmodium falciparum malaria in Cameroon. Hence, this study aimed to assess the effectiveness and safety of AS-AQ versus AL for home-based treatment of uncomplicated P. falciparum malaria among children 6-120 months in Yaoundé, Cameroon. METHODS: A two-arm, open-label, randomized, controlled trial comparing the equivalence of AS-AQ (experimental group) and AL (control group) was carried out from May 2019 to April 2020 at two secondary hospitals in Yaoundé. Participants were randomized to receive either AS-AQ or AL. After the first dose, antimalarial drugs were given at home, rather than under direct observation by a study staff. The conventional on-treatment and post-treatment laboratory and clinical evaluations were not done until day 3 of the full antimalarial treatment course. The evaluation of effectiveness was mainly based on per protocol polymerase chain reaction adjusted adequate clinical and parasitological response (PP PCR adjusted ACPR) on day 28 post-treatment. Safety was based on assessment of adverse events (AEs) and severe adverse events (SAEs) from day 1 to day 28. RESULTS: A total of 242 children were randomized to receive AS-AQ (n = 114) and AL (n = 128). The PP PCR adjusted day 28 cure rates were [AS-AQ = 96.9% (95% CI, 91.2-99.4) versus AL = 95.5% (95% CI, 89.9-98.5), P = 0.797]. Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever. CONCLUSIONS: This study demonstrated that AS-AQ and AL are effective and safe for home management of malaria in Yaoundé. The evidence from this study supports the parallel use of the two drugs in routine practice. However, the findings from this study do not describe the likely duration of antimalarial effectiveness in holoendemic areas where multiple courses of treatment might be required. TRIAL REGISTRATION: This study is a randomized controlled trial and it was retrospectively registered on 23/09/2020 at ClinicalTrials.gov with registration number NCT04565184.

Diabetes mellitus and tuberculosis, a systematic review and meta-analysis with sensitivity analysis for studies comparable for confounders.

INTRODUCTION: Meta-analyses conducted so far on the association between diabetes mellitus (DM) and the tuberculosis (TB) development risk did not sufficiently take confounders into account in their estimates. The objective of this systematic review was to determine whether DM is associated with an increased risk of developing TB with a sensitivity analyses incorporating a wider range of confounders including age, gender, alcohol consumption, smoke exposure, and other comorbidities. METHODS: Pubmed, Embase, Web of Science and Global Index Medicus were queried from inception until October 2020. Without any restriction to time of study, geographical location, and DM and TB diagnosis approaches, all observational studies that presented data for associations between DM and TB were included. Studies with no abstract or complete text, duplicates, and studies with wrong designs (review, case report, case series, comment on an article, and editorial) or populations were excluded. The odds ratios (OR) and their 95% confidence intervals were estimated by a random-effect model. RESULTS: The electronic and manual searches yielded 12,796 articles of which 47 were used in our study (23 case control, 14 cross-sectional and 10 cohort studies) involving 503,760 cases (DM or TB patients) and 3,596,845 controls. The size of the combined effect of TB risk in the presence of DM was OR = 2.3, 95% CI = [2.0-2.7], I2 = 94.2%. This statistically significant association was maintained in cohort (OR = 2.0, CI 95% = [1.5-2.4], I2 = 94.3%), case control (OR = 2.4, CI 95% = [2.0-2.9], I2 = 93.0%) and cross-sectional studies (OR = 2.5, CI 95% = [1.8-3.5], I2 = 95.2%). The association between DM and TB was also maintained in the sensitivity analysis including only studies with similar proportions of confounders between cases and controls. The substantial heterogeneity observed was mainly explained by the differences between geographic regions. CONCLUSIONS: DM is associated with an increased risk of developing latent and active TB. To further explore the role of DM in the development of TB, more investigations of the biological mechanisms by which DM increases the risk of TB are needed. REVIEW REGISTRATION: PROSPERO, CRD42021216815.

Incidence of adverse drug events among patients on second line anti-tuberculosis regimen in the littoral region of cameroon.

Background: An adverse drug event (ADE) is an injury resulting from medical intervention associated with a drug. This study assesses the incidence of ADEs among participants on second-line drugs for tuberculosis (TB) in Cameroon. Methods: This was a longitudinal observational study including 65 participants and carried out from January 2017 to December 2017. Markers of ADEs were obtained from creatinine, transaminase audiogram, and clinical data. Multivariate analysis was used to determine the association between predictors and ADEs. Results: Forty-eight (73.8%) of the 65 participants developed 72 ADEs. Fifty-four (75%), 11 (15.3%), and 7 (9.7%) of the 72 ADEs were classified as Grades 1, 2, and 3, respectively. Gastrointestinal disorders were most common (35 [46.6%]) followed by auditory injuries (16 [22.2%]), hepatotoxicity (11 [15.3%]), neurological disorders (6 [8.3%]), and kidney disorders (4 [5.6%]). The follow-up duration of this study was 11,250-person day (PDY). The incidence rate for ADEs was 4.3/1000 PDY and that for gastrointestinal disorders, auditory injuries, hepatotoxicity, neurological disorders, and kidney disorders was 3.1, 1.4, 1.0, 0.5, and 0.2 (/1000PDY), respectively. Kanamycin (65 [90.3%]), isoniazid (4 [5.6%]), and ethambutol (3 [4.2%]) were incriminated with ADEs. Most (29 [60.4%]) of the ADEs occurred during the first 2 months of drug initiation. There was an association between poor treatment outcome and ADEs (P = 0.04, odds ratio = 1.20, 95% confidence of interval = 0.21-6.80]. Conclusions: The incidence of ADEs is associated with several factors and most of them occurred during the intensive phase of treatment. Kanamycin was the most associated drug linked to ADEs requiring its replacement with a less toxic one.

Assessing Asymptomatic Malaria Carriage of Plasmodium falciparum and Non-falciparum Species in Children Resident in Nkolbisson, Yaoundé, Cameroon.

Malaria is still a threat to public health as it remains the first endemic disease in the world. It is a pervasive parasitic disease in tropical and subtropical regions where asymptomatic malaria infection among humans serves as a significant reservoir for transmission. A rapid and correct diagnosis is considered to be an important strategy in the control of the disease especially in children, who are the most vulnerable group. This study assessed the prevalence of asymptomatic malaria in children at the Nkolbisson health area in Yaoundé, Cameroon. A cross-sectional study design and a convenience sampling plan were used. A total of 127 participants were recruited after informed and signed consent from parents and/or guardians. Blood samples were collected by finger-pricking and venipuncture from children aged 6 months to 10 years and then screened for asymptomatic parasitemia by a rapid diagnostic test (RDT), light microscopy (LM) staining with Giemsa and 18S rRNA polymerase chain reaction (PCR) for speciation. The data were analyzed using SPSS version 20 software. The study identified 85 children who were positive from the PCR, 95 positive from the RDT and 71 from the LM, revealing a malaria prevalence of 66.9%, 74.8% and 55.9%, respectively. The prevalence was not observed to be dependent on the sex and age group of the participants. Plasmodium falciparum was the predominant species followed by Plasmodium malariae and then Plasmodium ovale. The RDT and LM had the same sensitivity (90.6%) with a slight difference in their specificity (RDT: 57.1%; LM: 54.8%). The RDT also demonstrated higher positive and negative predictive values compared with those of the LM.