Microbiology and Parasitology

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Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial
(Malaria journal., 2016) Mwaiswelo, Richard O.
Background: The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission set- tings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Methods: A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged =1 year, with the exception of pregnant and lactating women, were enrolled and treated with AL plus a single PQ dose (0.25 mg/kg) or AL alone under supervision. PQ was admin- istered together with the first AL dose. Clinical and laboratory assessments were performed at 0, 8, 24, 36, 48, 60, and 72 h and on days 7, 14, 21, and 28. The primary end-point was a polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) on day 28. Secondary outcomes included: fever and asexual parasitaemia clearance, proportion of patients with PCR-determined parasitaemia on day 3, and proportion of patients with Pfmdr1 N86Y and Pfcrt K76T on days 0, 3 and day of recurrent infection Results: Overall 220 patients were enrolled, 110 were allocated AL + PQ and AL, respectively. Parasite clearance by microscopy was fast, but PCR detectable parasitaemia on day 3 was 31/109 (28.4 %) and 29/108 (26.9 %) in patients treated with AL + PQ and AL, respectively (p = 0.79). Day 28 PCR-adjusted ACPR and re-infection rate was 105/105 (100 %) and 101/102 (99 %) (p = 0.31), and 5/107 (4.7 %) and 5/8 (4.8 %) (p = 0.95), in AL + PQ and AL arm, respec- tively. There was neither any statistically significant difference in the proportion of Pfmdr1 N86Y or Pfcrt K76T between treatment arms on days 0, 3 and day of recurrent infection, nor within treatment arms between days 0 and 3 or day 0 and day of recurrent infection. Conclusion: The new WHO recommendation of adding a single low-dose of PQ to AL did not compromise treat-ment outcome of uncomplicated P. falciparum malaria in Tanzania. Trial registration number NCT02090036
Africa’s Mushrooms: A Neglected Bioresource whose Time has Come
(Africa’s mushrooms, 2003) Mshigeni, Keto E.
Some of our readers, after assimilating the message contained in the Editorial of the last issue of our journal (Discovery and Innovation, Vol. 15 Number 1/ 2, pp. 1-7), “Surprises, scientific charm, socio-economic potential, and possibilities in the mushroom world”, wrote back, excited. One asked for more information on the Chinese mushroom farming experience with a view to exploring how Africa could also make it. Another wrote on the reticulately veiled mushroom collected from western Uganda, the edible Dictyophora mushroom, which had been mentioned in the previous Editorial. One who had read our other publications on Africa’s mushroom resources, had exciting novel information to share about one of Africa’s neglected wild mushrooms: Ganoderma
Anemia among Schoolchildren with Malaria and Soil-Transmitted Helminth Coinfections after Repeated Rounds of Mass Drug Administration in Muheza District, Tanzania
(The American journal of tropical medicine and hygiene, 2019) Mwaiswelo, Richard O.
A coinfection with malaria and soil-transmitted helminths (STHs) has been common among school-aged children in Tanzania. However, after a countrywide scaling up of interventions for malaria and STHs, there are limited data on the prevalence of malaria–STH coinfections and its effect on anemia in schoolchildren in Tanzania. We assessed the distribution and risk factors for malaria, STHs, and malaria–STH coinfections, and its relation to anemia among 445 primary schoolchildren in Muheza district. A semi-structured questionnaire was used to collect demographic characteristics of the children. Malaria rapid diagnostic test (mRDT) was used to diagnose malaria infection. Soil-transmitted helminths were diagnosed using the Kato–Katz technique. Primary outcome was anemia, defined as hemoglobin concentration < 11 g/dL. Chisquare (χ2) or Fisher’s exact tests, Kruskal–Wallis or t-test, and logistic models were used as appropriate. Overall, the prevalence of malaria, STHs, malaria–STH coinfection, and anemia were 18.4%, 6.1%, 1.6%, and 19.8%, respectively. Anemic children were more likely to have malaria (adjusted odds ratio [aOR] = 4.538, 95% CI: 2.189–9.409), whereas frequent use of bed nets was associated with reduced risk of malaria (aOR = 0.234, 95% CI: 0.130–0.42). On the other hand, not always using latrines and eating raw uncooked food increased the risk of STH infection. The prevalence of anemia was high and was associated with both malaria and malaria– STH infections, therefore calling for more integrated malaria–STH control approaches to target school-aged children.
Anemia and co-infection of P. falciparum and hookworm among school children in Kinondoni district Dar es Salaam Tanzania
(International Journal of Science and Research, 2019) Senkoro, Rehesina H.; Kabalimu, Titus K.
This was a cross-sectional study conducted in Kinondoni district from January to June 2015. The aim of the study was to determine the prevalence of co-infection of malaria and hookworm plus anemia in school-aged children. Stool and blood samples were collected from 332 children aged 6-14 years. Hemoglobin concentration (Hb) was determined by using portable HaemoCue. Giemsa- stained blood film was examined to detect malaria parasites while Kato Katz technique was used to detect hookworm ova. The Pearson’s chi-square, Student’s T-test, and Multivariate analysis were performed using SPSS version 20. The prevalence of malaria, hookworm, co-infection, and anemia were 13.5% 27.7% 7.5% and 22% respectively. The mean Hb was 10.51 g/dl (±1.31). Mean Hb in co-infected children was low compared to those with a single infection. The prevalence of co-infection was high among 6-11 years. Ascaris lumbricoides was another parasite that was isolated in this study. This study showed that anaemia, malaria and hookworm co-infection are prevalent in school-aged children and an intervention to address the rate of malaria, hookworm, and anemia in the study area should be considered.
Back to Africa: Tracing Dyslexia Genes in East Africa
(Reading and Writing, 2007) Kungulilo, Selemani
A sample of Swahili-speaking probands with reading difficulties was identified from a large representative sample of 1,500 school children in the rural areas of Tanzania. Families of these probands (n = 88) were invited to participate in the study. The proband and his/her siblings received a battery of reading-related tasks and performance on these tasks was recorded and treated as phenotypic data. Molecular-genetic analyses were carried out with 47 highly polymorphic markers spanning three previously identified regions of interest harboring susceptibility loci for reading difficulties: 2p, 6p, and 15q (DYX1–DYX3). The analyses revealed the involvement of these regions in the development of reading difficulties in Swahili. The linkage signals are especially pronounced for time (compared with error) indicators of reading difficulties. These findings are easily interpretable because in transparent languages such as Swahili deficits in reading are more related to the rate/speed of reading and reading-related processes than to the number of errors made. In short, the study incrementally advances the field by adding an understudied language and an understudied population to the variety of languages and populations in the field of molecular-genetic studies of reading difficulties.
Coelarthrum boergesenii (Rhodophycophyta, Rhodymeniales): a new record from Tanzania
(Botanica Marina, 1981) Mshigeni, Keto E.
A study has been conducted on specimens of a marine red alga collected by G. F. Papenfuss and R. F. Scagel in Tanzania during the International Indian Ocean Expedition in 1962. The thallus of the alga is small (2-3 cm tall), with a segmented construction and constrictions along the axes. Its branches arise mainly on the segments, and these often anastomose making it difficult to separate individual axes. Anatomically the axes have an epidermal layer ofsmall cells (3—5 μιη in diameter) and a cortex with outer smaller (8—20 μτη in diameter) and inner larger (70—150 μπ\in diameter) cells. Some of the inner cortical cells bear deeply staining gland cells, which are 9—12 μιη in diameter. The alga was identified as Coelarthrum boergesenii Weber-van Bosse, and is here reported as a first record of the genus in Tanzania.
COMT haplotypes suggest P2 promoter region relevance for schizophrenia
(Molecular psychiatry, 2004) Kungulilo, Selemani; Kajuna, Sylivester; Karoma, Nganyirwa J.
A recent study found, in a large sample of Ashkenazi Jews, a highly significant association between schizophrenia and a particular haplotype of three polymorphic sites in the catechol-Omethyl transferase, COMT, gene: an IVS 1 SNP (dbSNP rs737865), the exon 4 functional SNP (Val158Met, dbSNP rs165688), and a downstream SNP (dbSNP rs165599). Subsequently, this haplotype was shown to be associated with lower levels of COMT cDNA derived from normal cortical brain tissue, most likely due to cis-acting element(s). As a first step toward evaluating whether this haplotype may be relevant to schizophrenia in populations other than Ashkenazi Jews, we have studied this haplotype in 38 populations representing all major regions of the world. Adding to our previous data on four polymorphic sites in the COMT gene, including the Val158Met polymorphism, we have typed the IVS 1 rs737865 and 30 rs615599 sites and also included a novel IVS 1 indel polymorphism, yielding seven-site haplotype frequencies for normal individuals in the 38 globally distributed populations, including a sample of Ashkenazi Jews. We report that the schizophrenia-associated haplotype is significantly heterogeneous in populations worldwide. The three-site, schizophrenia-associated haplotype frequencies range from 0% in South America to 37.1% in Southwest Asia, despite the fact that schizophrenia occurs at roughly equal frequency around the world. Assuming that the published associations found between the exon 4 Val158Met SNP and schizophrenia are due to linkage disequilibrium, these new haplotype data support the hypothesis of a relevant cis variant linked to the rs737865 site, possibly just upstream in the P2 promoter driving transcription of the predominant form of COMT in the brain. The previously described HindIII restriction site polymorphism, located within the P2 promoter, varies within all populations and may provide essential information in future studies of schizophrenia.
Contributions on the Content and Nature of the Phycocoiloid from Laurencia papillosa (Forssk.) Greville (Rhodophyta, Ceramiales)
(Botanica Marina, 1977) Mshigeni, Keto E.
The content, infrared spectroscopy, total sulphate and optical rotation of the phycocolloid from Laurencia papillosa (Forssk.) Grevüle from Tanzania have been investigated. A phycocolloid yield of 33.6 ± 0-6% was obtained on a dry weight basis. The total sulphate content of the phycocolloid was 16.8 ± 0.4% and the optical rotation was found to be negative [a|D5 - 5.5 °. The phycocolloid was soluble in potassium Chloride. Its IR spectra showed absorptionpeaks more akin to -than -or -cairageenan. A detailed discussion of these findings is presented.
Contributions on the content and nature of the Phycocolloid from Halymenia venusta Boergesen (Rhodophyta, Cryptonemiales)
(Botanica Marina, 1977) Mshigeni, Keto E.
The phycocolloid from Halymenia venusta Boergesen has been studied and found to be a carrageenan which is morecloscly related to y-than k-carrageenan. A total phycocolloid yield of 59.0 ± 2.5 % on dry weight basis was obtained.The presence of a cold water-soluble phycocolloid in the thaüi of H. venusta was also discovered and its IR spectrum determined.
Contributions to the Embryology of Padina gymnospora (Phaeophyta, Dictyotales)
(Botanica Marina, 1978) Mshigeni, Keto E.
Abstract The pattern of tetraspore germination and early stages of development in Padina gymnospora (Kuetzing) Vickers (Phaeophyta, Dictyotales) have been investigated for a period of seven weeks. The early stages of development were äs earlier reported for other Dictyotales. However, new findings were found with respect to shoot differentiation. The erect shoots were initiated both from the meristematic activity of the ‘Central nodule' and from shoot initials which developed at intervals along the length of the rhizoids. The biological significance of the rhizoidal shoots is discussed
Developing a SNP panel for forensic identification of individuals
(Forensic science international, 2006) Kungulilo, Selemani; Kajuna, Sylivester; Karoma, Nganyirwa J.
Single nucleotide polymorphisms (SNPs) are likely in the near future to have a fundamental role in forensics in both human identification and description. However, considerable research is necessary to establish adequate scientific foundations for these applications. In the case of identification, because allele frequencies can vary greatly among populations, the population genetics of match probabilities is a critical issue. Some SNPs, however, show little allele frequency variation among populations while remaining highly informative. We describe here both an efficient strategy for identifying and characterizing such SNPs, and test that strategy on a broad representation of world populations. Markers with high heterozygosity and little frequency variation among African American, European American, and East Asian populations are selected for additional screening on seven populations that provide a sampling of genetic variation from the world's major geographical regions. Those with little allele frequency variation on the seven populations are then screened on a total of 40 populations (∼2100 individuals) and the most promising retained. The preliminary panel of 19 SNPs, from an initial selection of 195 SNPs, gives an average match probability of <10−7 in most of 40 populations studied and no greater than 10−6 in the most isolated, inbred populations. Expansion of this panel to ∼50 comparable SNPs should give match probabilities of about 10−15 with a small global range.
Diagnostic performance of malaria rapid diagnostic test and microscopy compared with PCR for detection of plasmodium falciparum infections among primary schoolchildren in kibiti district, eastern Tanzania: an area with moderate malaria transmission
(The American journal of tropical medicine and hygiene, 2019) Mwaiswelo, Richard O.
A substantial decline of malaria transmission intensity has been observed in sub-Saharan Africa over the past two decades and may affect the diagnostic performance of malaria rapid diagnostic test (mRDT) and microscopy. Diagnostic performance of histidine-rich protein II (HRP-II)/pan-lactate dehydrogenase (pLDH)–based mRDT and microscopy was evaluated against polymerase chain reaction (PCR) for the diagnosis of Plasmodium falciparum infection among 316 primary schoolchildren in Kibiti district, in 2016. Polymerase chain reaction detected more cases of P. falciparum infection than mRDT or microscopy. Using PCR as reference, the sensitivity and speciﬁcity of mRDT were 75.9% (95% CI = 62.8–86.1) and 96.9% (95% CI = 94.0–98.7), respectively, whereas that of microscopy were 63.8% (95% CI = 50.1–76.0) and 95.7% (95% CI = 92.5–97.9), respectively. Polymerase chain reaction and other molecular methods should be considered for use in schools and other epidemiological surveys as supplement to mRDT or microscopy.
Dihydroartemisinin-Piperaquine effectiveness for seasonal malaria chemoprevention In settings with extended seasonal malaria transmission in Tanzania
(Scientific Reports, 2024-01-25) Mwaiswelo, Richard O.
Effectiveness of dihydroartemisinin‑piperaquine (DP) as seasonal malaria chemoprevention (SMC) was assessed in Nanyumbu and Masasi Districts. Between March and June 2021, children aged 3–59 months were enrolled in a cluster randomized study. Children in the intervention clusters received a monthly, 3‑days course of DP for three consecutive months regardless of malaria infection status, and those in the control clusters received no intervention. Malaria infection was assessed at before the first‑round and at 7 weeks after the third‑round of DP in both arms. Malaria prevalence after the third‑round of DP administration was the primary outcome. Chi‑square tests and logistic regression model were used to compare proportions and adjust for explanatory variables. Before the intervention, malaria prevalence was 13.7% (161/1171) and 18.2% (212/1169) in the intervention and control clusters, respectively, p < 004. Malaria prevalence declined to 5.8% (60/1036) in the intervention clusters after three rounds of DP, and in the control clusters it declined to 9.3% (97/1048), p = 0.003. Unadjusted and adjusted prevalence ratios between the intervention and control arms were 0.42 (95%CI 0.32–0.55, p < 0.001) and 0.77 (95%CI 0.53–1.13, p = 0.189), respectively. SMC using DP was effective for control of malaria in the two Districts. Trial registration: NCT05874869, https://clinicaltrials.gov/ 25/05/2023
The distribution and most recent common ancestor of the 17q21 inversion in humans
(The American Journal of Human Genetics, 2010) Kungulilo, Selemani; Karoma, Nganyirwa J.; Kajuna, Sylivester
ABSTRACT The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an ~900 kb inversion found primarily in Europeans and Southwest Asians. We have identified 21 SNPs that act as markers of the inverted, i.e., H2, haplotype. The inversion is found at the highest frequencies in Southwest Asia and Southern Europe (frequencies of ~30%); elsewhere in Europe, frequencies vary from < 5%, in Finns, to 28%, in Orcadians. The H2 inversion haplotype also occurs at low frequencies in Africa, Central Asia, East Asia, and the Americas, though the East Asian and Amerindian alleles may be due to recent gene flow from Europe. Molecular evolution analyses indicate that the H2 haplotype originally arose in Africa or Southwest Asia. Though the H2 inversion has many fixed differences across the ~900 kb, short tandem repeat polymorphism data indicate a very recent date for the most recent common ancestor, with dates ranging from 13,600 to 108,400 years, depending on assumptions and estimation methods. This estimate range is much more recent than the 3 million year age estimated by Stefansson et al. in 2005.
Effects of the environment on developmental rates of sporelings of two Hypnea species (Rhodophyta: Gigartinales)
(Marine Biology, 1976) Mshigeni, Keto E.
Growth of sporelings of Hypnea cervicornis J. Agardh and H. chordacea Kuetzing in response to gradients of selected environmental factors has been investigated. The sporelings of H. cervicornis tolerated higher levels of the tested parameters (e.g. salinity and temperature) than those of H. chordacea. In all the treatments, the sporelings of H. cervicornis grew significantly faster than those of H. chordacea. The ecological and agronomic implications of these findings are discussed.
Efficacy of artesunate-amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria in mainland Tanzania.
(Malaria Journal, 2024-03-29) Mwaiswelo, Richard O.
Background: Diversification of artemisinin-based combination therapy (ACT) is suggested as one of the strategies that can be used to contain artemisinin resistance. Artesunate-amodiaquine (ASAQ) is one of the artemisinin-based combinations that can be used in the diversification strategy as an alternative first-line treatment for uncomplicated malaria in mainland Tanzania. There is however limited data on the efficacy of ASAQ in mainland Tanzania. This study assessed the efficacy of ASAQ for treatment of uncomplicated Plasmodium falciparum malaria in selected sentinel sites for therapeutic efficacy studies in mainland Tanzania. Methods: Between December 2018 and March 2020, children aged between 6 months and 10 years, attending at Nagaga, Mkuzi, and Mlimba primary health facilities, and with suspected uncomplicated malaria infection were screened for eligibility to participate in the study. Malaria infection was screened using microscopy. Children with uncomplicated P. falciparum monoinfection and who fulfilled all other inclusion criteria, and had none of the exclusion criteria, according to the World Health Organization (WHO) guidelines, were treated with ASAQ. Follow-up visits were scheduled on days 0, 1, 2, 3, 7, 14, 21, and 28 or on any day of recurrent infection for clinical and laboratory assessment. Polymerase chain reaction (PCR)-corrected cure rate on day 28 was the primary outcome. Results: A total of 264 children, 88 in each of the three study sites (Mlimba, Mkuzi and Nagaga health facilities) were enrolled and treated with ASAQ. The ASAQ PCR-corrected cure rate was 100% at all the three study sites. None of the participants had early treatment failure or late clinical failure. Furthermore, none of the participants had a serious adverse event. Conclusion: ASAQ was highly efficacious for the treatment of uncomplicated P. falciparum malaria in mainland Tanzania, therefore, it can be deployed as an alternative first-line treatment for uncomplicated malaria as part of diversification strategy to contain the spread of partial artemisinin resistance in the country.
Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis.
(Journal of Infectious Disease, 2020) Mwaiswelo, Richard O.
Background Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combina-tion with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falcip-arum, several single-site studies have been conducted to assess efficacy. Methods An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combina-tion with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte car-riage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. Results In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most ap-parently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17–.28 and OR, 0.12; 95% CI, .08–.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P= .010 for day 7). Addition of 0.25 mg/kg PQ was associ-ated with near complete prevention of transmission to mosquitoes. Conclusions Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP. Keywords. single low-dose primaquine; Plasmodium falciparum; gametocytemia.
Evaluation of residual submicroscopic Plasmodium falciparum parasites 3 days after initiation of treatment with artemisinin-based combination therapy.
(Malaria Journal, 2020) Mwaiswelo, Richard O.
Plasmodium falciparum resistance against artemisinin has not emerged in Africa; however, there are reports of the presence of polymerase chain reaction-determined residual submicroscopic parasitaemia detected on day 3 after artemisinin-based combination therapy (ACT). These residual submicroscopic parasites are thought to represent tolerant/resistant parasites against artemisinin, the fast-acting component of the combination. This review focused on residual submicroscopic parasitaemia, what it represents, and its significance on the emergence and spread of artemisinin resistance in Africa. Presence of residual submicroscopic parasitemia on day 3 after treatment initiation leaves question on whether successful treatment is attained with ACT. Thus there is a need to determine the potential public health implication of the PCR-determined residual submicroscopic parasitaemia observed on day 3 after ACT. Robust techniques, such as in vitro cultivation, should be used to evaluate if the residual submicroscopic parasites detected on day 3 after ACT are viable asexual parasites, or gametocytes, or the DNA of the dead parasites waiting to be cleared from the circulation. Such techniques would also evaluate the transmissibility of these residual parasites.
The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination
(Annals of human genetics, 2004) Kungulilo, Selemani; Kajuna, Sylivester; Karoma, Nganyirwa J.
Summary The catalytic deficiency of human aldehyde dehydrogenase 2 (ALDH2) is caused by a nucleotide substitution (G1510A; Glu487Lys) in exon 12 of the ALDH2 locus. This SNP, and four non‐coding SNPs, including one in the promoter, span 40 kb of ALDH2; these and one downstream STRP have been tested in 37 worldwide populations. Only four major SNP‐defined haplotypes account for almost all chromosomes in all populations. A fifth haplotype harbours the functional variant and is only found in East Asians. Though the SNPs showed virtually no historic recombination, LD values are quite variable because of varying haplotype frequencies, demonstrating that LD is a statistical abstraction and not a fundamental aspect of the genome, and is not a function solely of recombination. Among populations, different sets of tagging SNPs, sometimes not overlapping, can be required to identify the common haplotypes. Thus, solely because haplotype frequencies vary, there is no common minimum set of tagging SNPs globally applicable. The Fst values of the promoter region SNP and the functional SNP were about two S.D. above the mean for a reference distribution of 117 autosomal biallelic markers. These high Fst values may indicate selection has operated at these or very tightly linked sites.
Field Cultivation of Hypnea (Rhodophyta) Spores for Carrageenan: Prospects and Problems
(Botanica Marina, 1976) Mshigeni, Keto E.
Carpospores and tetraspores ofHypnea cervicornis J, Agardh have been cultivated in the fieid. These developed intoadult fronds in thiee months. This implies that where nutrients or other environmental factors are not limiting, it ispossible to raise four harvestable crops of Hypnea from spores per year, Since carpospores gave rise to tetrasporo-phytes and tetraspores produced gametophytes, it was concluded that the life history of the species is of the Poly-siphonia-type

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