Implementing malaria control in South Africa, Eswatini and southern Mozambique during the COVID-19 pandemic.

The COVID-19 pandemic has strained healthcare delivery systems in a number of southern African countries. Despite this, it is imperative that malaria control and elimination activities continue, especially to reduce as far as possible the number and rate of hospitalisations caused by malaria. The implementation of enhanced malaria control/elimination activities in the context of COVID-19 requires measures to protect healthcare workers and the communities they serve. The aim of this review is therefore to present innovative ideas for the timely implementation of malaria control without increasing the risk of COVID-19 to healthcare workers and communities. Specific recommendations for parasite and vector surveillance, diagnosis, case management, mosquito vector control and community outreach and sensitisation are given.

Maintaining focus on administering effective malaria treatment during the COVID-19 pandemic.

As September marks the start of the malaria season in South Africa (SA), it is essential that healthcare professionals consider both COVID- 19 and malaria when a patient who lives in or has recently travelled to a malaria area presents with acute febrile illness. Early diagnosis of malaria by either a rapid diagnostic test or microscopy enables prompt treatment with the effective antimalarial, artemether-lumefantrine, preventing progression to severe disease and death. Intravenous artesunate is the preferred treatment for severe malaria in both children and adults. Adding single low-dose primaquine to standard treatment is recommended in endemic areas to block onward transmission. Use of the highly effective artemisinin-based therapies should be limited to the treatment of confirmed malaria infections, as there is no clinical evidence that these antimalarials can prevent or treat COVID-19. Routine malaria case management services must be sustained, in spite of COVID-19, to treat malaria effectively and support SA's malaria elimination efforts.

Implementing malaria control in South Africa, Eswatini and southern Mozambique during the COVID-19 pandemic

The COVID-19 global pandemic reached South Africa (SA), Mozambique and Eswatini in March 2020.[1] Since then an exponential increase in SARS-CoV-2 infections has severely stretched SA's healthcare system, especially in terms of in-hospital treatment of severe cases. The impact of COVID-19 in Mozambique and Eswatini at the time of writing has been comparatively mild, but is increasing. It is therefore imperative to reduce as far as possible the number and rate of hospitalisations caused by trauma and other diseases, including malaria. Malaria incidence in SA is seasonal and peaks in the wetter summer months, especially during January to April.[2] Although malaria incidence in SA is currently low, the risk of outbreaks is always present, with the most recent having occurred in 2017 and, at a more localised level in Limpopo Province, in 2019. The reasons for these latest outbreaks are varied and include unusually high rainfall and cross-border movement of migrant populations, fuelling local transmission. These issues are particularly pertinent to COVID-19 in SA's malaria-affected districts. They highlight the importance of mitigating factors contributing to high malaria incidence and consequent hospitalisations, which may be further exacerbated by COVID-19/malaria coinfections and the re-opening of SA's borders with those neighbouring countries with higher malaria transmission intensities.

Spotted fever rickettsiosis in South Africa: Evaluation of laboratory diagnostic capacity and inter-laboratory comparison of serological testing.

BACKGROUND: Spotted fever rickettsiosis, also known as tick bite fever (TBF), is a common infectious disease in South Africa (SA). Although the diagnosis of TBF is often based on clinical grounds only, laboratory testing is important to confirm the diagnosis and can contribute to case management in the light of a myriad of differential diagnoses, and in complicated cases. OBJECTIVES: To report on the availability and scope of laboratory tests for investigating suspected cases of TBF in SA, and the outcome of an inter-laboratory comparison (ILC) conducted for serological tests. METHODS: A self-administered questionnaire was circulated to major pathology laboratories in SA to determine what TBF tests they offered for TBF investigation. In addition, a clinical panel was provided to willing laboratories in order to perform an ILC of the serological tests. RESULTS: Serological tests for TBF were available from five laboratories serving both the private and state medical sectors in SA. There was no standardised testing platform or result interpretation across the different laboratories. Polymerase chain reaction (PCR) tests were less frequently available, and not available to state-operated facilities. The outcome of the ILC indicated varied performance and interpretation of serological results for TBF. CONCLUSIONS: Laboratory investigation for TBF is routinely and widely available in SA. Both serological and PCR-based methods were varied, and the lack of standardisation and interpretation of tests needs to be addressed to improve the overall quality of TBF diagnosis in SA. The utility of ILC to identify problem areas in serological testing for TBF is highlighted, and laboratories in SA are encouraged to use it to improve the quality of testing.

Successfully controlling malaria in South Africa.

Following major successes in malaria control over the past 75 years, South Africa is now embarking on a malaria elimination campaign with the goal of zero local transmission by the year 2018. The key control elements have been intensive vector control, primarily through indoor residual spraying, case management based on parasitological diagnosis using evidence-based drug policies with artemisinin-based combination therapy since 2001, active health promotion in partnership with communities living in the malaria transmission areas, and cross-border collaborations. Political commitment and long-term funding for the malaria control programme have been a critical component of the programme's success. Breaking the cycle of transmission through strengthening of active surveillance using sensitive molecular tests and field treatment of asymptomatic persons, monitoring for antimalarial drug resistance and insecticide resistance, strengthening cross-border initiatives, and ongoing programme advocacy in the face of a significant decrease in disease burden are key priorities for achieving the elimination goal.

Anthrax as an example of the One Health concept.

Anthrax is a peracute, acute or subacute multispecies bacterial infection that occurs on many continents. It is one of the oldest infectious diseases known; the biblical fifth and sixth plagues (Exodus chapters 7 to 9) that affected first livestock and then humans were probably anthrax. From the earliest historical records until development of an effective vaccine midway through the 20th Century, anthrax was one of the foremost causes of uncontrolled mortality in cattle, sheep, goats, horses and pigs, with 'spill over' into humans, worldwide. With the development of the Sterne spore vaccine, a sharp decline in anthrax outbreaks in livestock occurred during the 1930-1980 era. There were successful national vaccination programmes in many countries during this period, complemented by the liberal use of antibiotics and the implementation of quarantine regulations and carcass disposal. However, a resurgence of this disease in livestock has been reported recently in some regions, where complacency and a false sense of security have hindered vaccination programmes. The epidemiology of anthrax involves an environmental component, as well as livestock, wildlife and human components. This makes anthrax an ideal example for discussion in the One Health context. Many outbreaks of anthrax in wildlife are undetected or unreported, owing to surveillance inadequacies and difficulties. Human disease is generally acquired accidentally during outbreaks of anthrax in domestic livestock and wildlife. The exception is deliberate targeting of humans with anthrax in the course of biowarfare or bioterrorism.

Re-defining the extent of malaria transmission in South Africa: implications for chemoprophylaxis.

BACKGROUND: Malaria case numbers reported in South Africa have reduced considerably over the last decade, necessitating a revision of the national risk map to guide malaria prevention, including the use of chemoprophylaxis. OBJECTIVES: To update the national malaria risk map based on recent case data and to consider the implications of the new transmission profile for guiding prophylaxis. METHODS: The geographical distribution of confirmed malaria cases detected both passively and actively over the last six malaria seasons was used to redefine the geographic distribution and intensity of malaria transmission in the country. RESULTS: The national risk map was revised to reflect zones of transmission reduced both in their extent and their intensity. Most notably, the area of risk has been reduced in the north-western parts of Limpopo Province and is limited to the extreme northern reaches of KwaZulu-Natal Province. Areas previously considered to be of high risk are now regarded to be of moderate risk. CONCLUSION: Chemoprophylaxis is now only recommended from September to May in the north-eastern areas of Limpopo and Mpumalanga Provinces. The recommended options for chemoprophylaxis have not changed from mefloquine, doxycycline or atovaquone-proguanil.

Case management of malaria: diagnosis.

Laboratory diagnosis of malaria in South Africa has traditionally relied on microscopic examination of stained blood films. More recently, rapid diagnostic tests (RDTs) have been introduced into routine use, and molecular methods like polymerase chain reaction are useful in certain situations. As with all laboratory tests, each technique has its advantages and disadvantages. Microscopy and RDTs, if appropriately quality assured, are adequate for clinical case management. For elimination, active surveillance will need to be expanded substantially, with wider use of more sensitive diagnostic nucleic acid amplification techniques, and/or serology. To facilitate surveillance activities, techniques suitable for field or near-field use would be ideal. A long-running external quality assessment programme in South Africa has shown some deficiencies in the quality of malaria diagnosis in routine laboratories. Quality systems across the spectrum of diagnostic facilities in South Africa need strengthening, to ensure progress towards elimination. 

Genetic characterization of Cryptosporidium spp. in diarrhoeic children from four provinces in South Africa.

The diversity of Cryptosporidium at species, subtype family and subtype level in diarrhoeic children was investigated in four provinces in South Africa. A total of 442 stool samples from children <5 years of age were collected under a large rotavirus surveillance programme and analysed by Ziehl-Neelsen acid-fast staining. Fifty-four (12.2%) were positive for Cryptosporidium, of which 25 were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and DNA sequence analyses of the 18S rRNA gene. The majority of genotyped specimens were identified as C. hominis (76%), and a high genetic diversity was found with five different C. hominis subtype families (Ia, Ib, Id, Ie and If). Cryptosporidium parvum was found in 20% of the isolates, and three subtype families were identified (IIc, IIe and IIb), with subtype family IIc being the most common. One specimen was identified as C. meleagridis of the subtype family IIId. These results are in accordance with findings from other developing countries and report for the first time the presence in South Africa of C. meleagridis, various subtypes of C. parvum and the subtype family Ie of C. hominis. The results suggest that C. hominis and anthroponotic C. parvum subtypes are the major cause of cryptosporidiosis in South Africa. Further molecular studies are needed to better understand the epidemiology and public health importance of Cryptosporidium in humans in South Africa.

Malaria control in South Africa - challenges and successes.

Control measures have substantially reduced the historical distribution of malaria in South Africa; the country's population currently at risk for contracting malaria is approximately 4.3 million, predominantly in the northern and eastern border areas. The major strategies for malaria control are vector control through indoor residual spraying, case management, disease surveillance, epidemic preparedness and response, and public awareness. There has been a significant and sustained decrease in malaria case notifications since 2000, as a result of intensive indoor residual spraying including the use of DDT to combat insecticide-resistant Anopheles funestus; the introduction of artemisinin combination therapy; and the Lebombo Spatial Initiative, a cross-border collaboration targeting malaria in eastern Swaziland, southern Mozambique and northern KwaZulu-Natal (KZN). Rapid malaria antigen detection tests are widely used for diagnosis at primary health care level. HIV-malaria co-infected patients who are malaria non-immune are at risk for severe malaria. Renal failure has been identified as a particular complication in this group of patients. Despite successes in malaria control in South Africa, many challenges remain.

Tick bite fever and Q fever - a South African perspective.

Tick bite fever (TBF) and Q fever are zoonotic infections, highly prevalent in southern Africa, which are caused by different genera of obligate intracellular bacteria. While TBF was first described nearly 100 years ago, it has only recently been discovered that there are several rickettsial species transmitted in southern Africa, the most common of which is Rickettsia africae. This helps to explain the highly variable clinical presentation of TBF, ranging from mild to severe or even fatal, that has always been recognised. Q fever, caused by Coxiella burnetii, is a protean disease that is probably extensively under-diagnosed. Clinically, it also shows a wide spectrum of severity, with about 60% of cases being clinically inapparent. Unlike TBF, Q fever may cause chronic infection, and a post-Q fever chronic fatigue syndrome has been described. The molecular pathophysiology of these diseases provides insight into different strategies that intracellular parasites may use to survive and cause disease. While newer macrolide and quinolone antibiotics show activity against these pathogens and may be useful in young children and pregnant women, the treatment of choice for acute infection in both diseases is still tetracycline-group antibiotics. Chronic Q fever remains challenging to treat.

High rate of Bartonella henselae infection in HIV-positive outpatients in Johannesburg, South Africa.

The emerging opportunistic pathogen Bartonella henselae has a wide range of clinical presentation, which includes, particularly, bacillary angiomatosis. This non-random pilot survey of outpatients attending HIV clinics in Johannesburg, South Africa, sampled 188 patients, in whom there was a 10% prevalence of Bartonella bacteraemia, as determined by nested polymerase chain reaction.

Effect of human immunodeficiency virus infection on episodes of diarrhea among children in South Africa.

BACKGROUND: Infection with HIV is increasing among children in South Africa. Diarrhea is a common cause of morbidity and mortality in Africa, and some studies have shown that HIV-infected children have episodes of severe diarrhea with higher mortality than HIV-uninfected children. OBJECTIVES: To compare the severity, pathogens and outcome of diarrhea in HIV-infected and uninfected children. METHODS: We studied 181 children ages 3 months to 4 years admitted for gastroenteritis to the Chris Hani Baragwanath Hospital in Soweto, South Africa. Demographic details of the children were recorded, as were the details of the episode of diarrhea. Stools specimens were collected and sent for microbiologic evaluation. The clinical course of the child's admission was recorded. Children were diagnosed as being infected with HIV if they tested positive by HIV enzyme-linked immunosorbent assay (ELISA) and were >15 months of age, or if they were ELISA-positive, were < 15 months of age and had clinical signs of HIV infection. RESULTS: Of the 176 children with an HIV ELISA result, 31 (17.6%) were classified as HIV-infected. More HIV-infected children were malnourished (80.6% vs. 39.5%, P < 0.001) and more likely to have had prolonged diarrhea (16.1% vs. 5.9%, P = 0.07) compared with HIV-uninfected children. HIV-infected children had a higher rate of a codiagnosis of pneumonia (43.3% vs. 9.2%, P < 0.0001) and were more likely to require a hospital stay of >4 days (prevalence odds ratio, 5.11; 95% confidence interval, CI 1.49 to 17.52). There were no significant differences in stool pathogens or in the level of dehydration on admission between the HIV-infected and uninfected children. CONCLUSION: HIV-infected children have the same spectrum of enteric pathogens as uninfected children but require more attention because of malnutrition and comorbidity.

Molecular characterization of a hepatitis E virus isolate from Namibia.

Hepatitis E virus (HEV) causes sporadic and epidemic acute viral hepatitis in many developing countries. In Africa, hepatitis E has been documented by virus detection (reverse transcriptase polymerase chain reaction, RT-PCR) in Egypt, Chad, Algeria, Morocco and Tunisia. Cases of presumptive hepatitis E also have been documented by detection of antibody to HEV in the Sudan, Kenya, Ethiopia, Somalia, Djibouti and South Africa. Recently, we reported the recovery of 9 isolates of HEV from feces collected during an outbreak of jaundice in Namibia. These specimens were stored frozen for many years at the South African Institute for Medical Research awaiting new methods to determine the etiology of jaundice. HEV genomic sequences were detected by antigen-capture RT-PCR with primers that amplified 2 independent regions of the HEV genome (ORF-2 and ORF-3). To further characterize the HEV 83-Namibia isolates, we determined the nucleotide (nt) sequence of the 3' end of the capsid gene (296 of 1, 980 nt in ORF-2) and ORF-3 for 1 isolate. The capsid gene sequence shared 86% identity with the prototype Burma strain and up to 96% identity with other African strains at the (nt) level, and 99% identity with Burma or other Africa strains at the amino acid level. A 188 (nt) fragment amplified from ORF-3 was also highly homologous to other HEV but was too short for meaningful comparison. Phylogenetic analysis indicated that HEV 83-Namibia is closely related to other African isolates, and differs from Burmese, Mexican and Chinese HEV. These data link the HEV causing the 1983 Namibia outbreak to more recent HEV transmission in northern and sub-Saharan Africa, suggesting this subgenotype of HEV is firmly established throughout the continent.

Chloroquine-resistant isolates of Plasmodium falciparum with alternative CG2 omega repeat length polymorphisms.

A particular polymorphism in the cg2 gene has previously been linked to chloroquine resistance in reference isolates of Plasmodium falciparum. To assess the association of this polymorphism with chloroquine resistance in field specimens of P. falciparum, we analyzed the omega repeat region of the cg2 gene in 47 isolates of P. falciparum collected in the Ingwavuma District of northern KwaZulu-Natal, South Africa. Polymerase chain reaction (PCR) primers, which were designed to amplify the region of DNA surrounding the omega repeat, were used to obtain omega repeat PCR products from the field isolates. The PCR product for each isolate varied in length, depending on the number of cg2 omega repeats for that isolate. We found that several in vivo and in vitro chloroquine-resistant isolates of P. falciparum did not have the expected 16 omega repeats. These results suggest that the link between the cg2 polymorphism and chloroquine resistance identified previously may not apply in all malarious areas.

Unusual case of Acanthamoeba polyphaga and Pseudomonas aeruginosa keratitis in a contact lens wearer from Gauteng, South Africa.

Acanthamoeba species can cause a chronic, progressive ulcerative keratitis of the eye which is not responsive to the usual antimicrobial therapy and is frequently mistaken for stromal herpes keratitis. An unusual case of coinfection with Acanthamoeba polyphaga and Pseudomonas aeruginosa as causes of corneal keratitis in a contact lens wearer from Gauteng, South Africa, is reported. These two pathogens have previously been assumed to be selectively exclusive. Cysts of the isolated acanthameba tolerated an incubation temperature of 40 degrees C, indicating a pathogenic species. This case highlights the importance of culture methods in the diagnosis of corneal infection and the choice of treatment regimen. The patient's history of careless contact lens-disinfecting habits emphasizes the need to adhere strictly to recommended methods of contact lens care.